The goal of any plant breeding program is to maximize genetic gain for traits of interest. In classical quantitative genetics, the genetic gain can be obtained
from what is known as Breeders equation. In the past, only phenotypic data was used to compute the genetic gain. The advent of genomic prediction has opened the
door to the utilization of dense markers for estimating genomic breeding values or GBV. The salient feature of
genomic prediction is the possibility to carry out genomic selection with the assistance of the kinship matrix, hence, improving the prediction accuracy and
accelerating the breeding cycle. However, estimates of GBV as such do not provide the full information on the
number of entries to be selected as in the classical response to selection. In this paper, we use simulation, based on a fitted mixed model for genomic prediction
in a multi-environmental framework, to answer two typical questions of a plant breeder: (1) How many entries need to be selected to have a defined probability of
selecting the truly best entry from the population; (2) What is the probability of obtaining the truly best entries when some top-ranked entries are selected.
Population bottlenecks are common in nature, and they can impact the rate of adaptation in evolving populations. On the one hand, each bottleneck reduces the
genetic variation that fuels adaptation. On the other hand, fewer founders can undergo more generations and leave more descendants in a resource-limited
environment, which allows surviving beneficial mutations to spread more quickly. Here we investigate the impact of repeated bottlenecks on the dynamics of
adaptation in experimental populations of Escherichia coli. We propagated 48 populations under four dilution regimes (2×, 8×, 100×, and 1000×), all
reaching the same final size each day, for 150 days. A simple model in which adaptation is limited by the supply rate of beneficial mutations predicts that fitness
gains should be maximized with ~8× dilutions. The model also assumes that selection acts only on the overall growth rate and is otherwise identical across dilution
regimes. However, we found that selection in the 2× regime was qualitatively different from the other treatments. Moreover, we observed earlier and greater fitness
gains in the populations subjected to 100- and 1000× dilutions than in those that evolved in the 8× regime. We also ran simulations using parameters estimated
independently from a long-term experiment using the same ancestral strain and environment. The simulations produced dynamics similar to our empirical results under
these regimes, and they indicate that the simple model fails owing to the assumption that the supply of beneficial mutations limits adaptation.
Cancer is one of the most threatening diseases to humans. Understanding the evolution of cancer genes is helpful for therapy management. However, systematic
investigation of the evolution of cancer driver genes is sparse. Using comparative genomic analysis, population genetics analysis and computational molecular
evolutionary analysis, we detected the evolution of 568 cancer driver genes of 66 cancer types across the primate phylogeny (long timescale selection), and in
modern human populations from the 1000 human genomics project (recent selection). We found that recent selection pressures, rather than long timescale selection,
significantly affect the evolution of cancer driver genes in humans. Cancer driver genes related to morphological traits and local adaptation are under positive
selection in different human populations. The African population showed the largest extent of divergence compared to other populations. It is worth noting that the
corresponding cancer types of positively selected genes exhibited population-specific patterns, with the South Asian population possessing the least numbers of
cancer types. This helps explain why the South Asian population usually has low cancer incidence rates. Population-specific patterns of cancer types whose driver
genes are under positive selection also give clues to explain discrepancies of cancer incidence rates in different geographical populations, such as the high
incidence rate of Wilms tumour in the African population and of Ewing9s sarcomas in the European population. Our findings are thus helpful for understanding cancer
evolution and providing guidance for further precision medicine.
Dispersal has three major effects on adaptation. First, the gene flow mixes alleles adapted to different environments, potentially hindering (swamping)
adaptation. Second, it inflates genetic variance: this aids adaptation to spatially (and temporally) varying environments but if selection is hard, it lowers the
mean fitness of the population. Third, neighbourhood size, which determines how weak genetic drift is, increases with dispersal—when genetic drift is strong,
increase of neighbourhood size with dispersal aids adaptation. In this note I focus on the role of dispersal in environments which change smoothly across space,
and when local populations are quite small such that genetic drift has a statistically-significant effect. Using individual-based simulations, I show that in small
populations, even leptokurtic dispersal benefits adaptation, by reducing the power of genetic drift. This has implications for management of small marginal
populations: increased gene flow appears beneficial as long as adaptations involves a quantitative, rather than a discrete, trait. However, heavily leptokurtic
dispersal will swamp continuous adaptation along steep environmental gradients so that only patches of locally adapted subpopulations remain.
Multiple large-bodied species went extinct during the Pleistocene. Changing climates and/or human hunting are the main hypotheses used to explain
these extinctions.
We studied the causes of Pleistocene extinctions in the Southern Levant, and
their subsequent effect on local hominin food spectra, by examining faunal remains in archaeological sites across the last 1.5 million years. We examined whether
climate and climate changes, and/or human cultures, are associated with these declines. We recorded animal abundances published in the literature from 133
stratigraphic layers, across 58 Pleistocene and Early Holocene archaeological sites,
in the Southern Levant. We used linear regressions and mixed models to assess the weighted mean mass of faunal assemblages through time and whether it was
associated with temperature, paleorainfall, or paleoenvironment (C3
vs. C4 vegetation).
We found that weighted mean body mass declined log-linearly through time. Mean hunted animal masses 10,500 years ago, were only 1.7% of those 1.5 million years
ago. Neither body size at any period, nor size change from one layer to the next, were related to global temperature or to temperature changes. Throughout the
Pleistocene, new human lineages hunted statistically-significantly smaller prey than the preceding ones.
This suggests that humans extirpated megafauna throughout the Pleistocene, and when the largest species were depleted the next-largest were targeted.
Technological advancements likely enabled subsequent human lineages to effectively hunt smaller prey replacing larger species that were hunted to extinction or
until they became exceedingly rare.
[Keywords: Levant, megafauna, early humans, hunting, Pleistocene, Quaternary, climate]
The notion that men are more variable than women has become embedded into
scientific thinking. For mental traits like personality, greater male variability has been partly attributed to biology, underpinned by claims that there is
generally greater variation among males than females in non-human animals due to stronger sexual selection on males. However, evidence for greater male variability is limited to morphological traits, and there is little information
regarding sex differences in personality-like behaviours for non-human animals.
Here, we meta-analysed sex differences in means and variances for over 2,100 effects (204 studies) from 220 species (covering 5 broad taxonomic groups) across 5
personality traits: boldness, aggression, activity, sociality and exploration. We also tested if sexual size dimorphism, a proxy for sex-specific sexual selection, explains variation in the
magnitude of sex differences in personality.
We found no statistically-significant differences in personality
between the sexes. In addition, sexual size dimorphism did not explain variation in the magnitude of the observed sex differences in the mean or variance in personality for any taxonomic group.
In sum, we find no evidence for widespread sex differences in variability in non-human animal personality.
[Keywords: sexual selection, personality, behaviour, sex differences, variability, shared traits, meta-analysis, sexual size dimorphism,
heterogamety, greater male variability hypothesis]
Background: Dog breeds are known for their distinctive body
shape, size, coat color, head type and behaviors, features that are relatively similar across members of a breed. Unfortunately, dog breeds are also characterized
by distinct predispositions to disease. We explored the relationships between inbreeding, morphology and health using genotype based inbreeding estimates, body weight and insurance data for morbidity.
Results: A large dataset (227 breeds; dataset 1) of median heterozygosity values (H) was obtained through commercial DNA testing of 49,378 dogs…In order to
investigate the effect of inbreeding level on health we utilized breed-based health data from Agriapet insurance…The average inbreeding based on genotype across 227 breeds was Fadj = 0.249 (95% CI 0.235–0.263).
There were statistically-significant differences in morbidity between
breeds with low and high inbreeding (H = 16.49, p = 0.0004). There was also a statistically-significant difference in morbidity between brachycephalic breeds and non-brachycephalic breeds (p = 0.0048) and between
functionally distinct groups of breeds (H = 14.95 p < 0.0001). Morbidity was modeled using robust regression analysis and both body weight (p
< 0.0001) and inbreeding (p = 0.013) were statistically-significant (R2 = 0.77).
Smaller less inbred breeds were healthier than larger more inbred breeds.
Conclusions: In this study, body size and inbreeding along with deleterious morphologies contributed to increases in necessary health care in
dogs.
…The inbreeding values within dog breeds were very high, with the mean being 0.24, just below the coefficient of inbreeding obtained from breeding full
siblings. The breeds with low inbreeding included recent cross breeds (Tamaskan Dog, Barbet and Australian Labradoodle) and landrace breeds (Danish-Swedish
Farmdog, Mudi and Koolie), supporting the notion that high inbreeding is a result of closed stud books or small numbers of founders or both. It also demonstrates
that it is possible to have consistent breed type without inbreeding.
Similar to another recent study, brachycephalic dogs require more veterinary care than non-brachycephalic dogs.34 In addition, we identified
that FCI group 2 breeds required the highest average number of veterinary care events. This group includes the larger
molossoid dog breeds which others have previously identified as having higher mortality32, 44. The primitive FCI group 5 breeds had the lowest average morbidity of all the groups, which has not been reported previously, except for the
Norrbottenspitz breed.45 This may be, in part, due to the large number of primitive breeds for which there is insurance data available in our data set,
while other studies may not have had health data available for these breeds.
There were interesting exceptions to the correlation of inbreeding and health. The Border terrier, Basenji, Collie, and English setter breeds have high
inbreeding but low morbidity. Likewise, the Malinois, Pomeranian and Russian Tsvetnaya Bolonka (Russian Toy) have lower inbreeding and high morbidity. These
example breeds are neither brachycephalic nor particularly known for extreme morphologies. In the case of healthy breeds with high inbreeding, it may be possible
that these breeds have been purged of deleterious alleles as has happened with inbred mouse strains [Mouse genetics concepts and applications,
Silver 1995]. In the opposite situation (lower inbreeding and high morbidity), the recorded morbidities could be high allele frequency Mendelian diseases or
potentially conditions linked to phenotypes under selection in the breed. These discrepancies could also exist due to population differences between the insurance
data and the inbreeding data.
…One must consider that the majority of dog breeds displayed high levels of inbreeding well above what would be considered safe for either humans or wild animal
populations. The effects of inbreeding on overall fitness have been demonstrated experimentally using mice, where an overall reduction in fitness between mice with
F = 0.25 compared to F = 0 was determined to be 57%.54 While this high level of inbreeding was less relevant to many captive and wild species, it is
highly relevant to purebred dogs, based on the average inbreeding identified in this study. However the rate of inbreeding between these mouse experiments and what
has occurred in dogs breeds is not the same and could have an effect on health. In humans, modest levels of inbreeding (3–6%) were shown to be associated with
increased prevalence of late onset complex diseases 55 as well as other types of inbreeding depression.11 These findings in other species combined with the incredibly strong breed predispositions to complex
diseases like cancers and autoimmune diseases highlight the potential relevance of high inbreeding in dogs to their health.
Theories on the evolutionary origins of altruistic behavior have a long history and have become a canonical part of the theory of evolution. Nevertheless, the
mechanisms that allow altruism to appear and persist are still incompletely understood. The spatial structure of populations is known to be an important
determinant. In both theoretical and experimental studies, much attention has been devoted to populations that are subdivided into discrete groups. Such studies
typically imposed the structure and dynamics of the groups by hand.
Here, we instead present a simple individual-based model in which organisms spontaneously self-organize into spatially separated colonies that themselves
reproduce by binary fission and hence behave as Darwinian entities in their own right. Using software to automatically track the rise and fall of colonies, we are
able to apply formal theory on multilevel selection and
thus quantify the within-group and among-group dynamics.
This reveals that individual colonies inevitably succumb to defectors, resulting in within-colony “tragedies of the commons”. Even so, altruism persists in the population because more altruistic colonies reproduce more frequently. The
emergence of the colonies themselves depends crucially on the length scales of motility, altruism, and competition.
This reconfirms the general relevance of these scales for social evolution, but also stresses that their impact can only be understood fully in the light of the
emergent eco-evolutionary spatial patterns. The results also demonstrate that emergent spatial population patterns can function as a starting point for transitions
of individuality.
Late-onset Alzheimers Disease (LOAD) pathology is rare in our closest living evolutionary relatives
(chimpanzees), which also express much lower microglial levels of CD33(Siglec-3), a myelomonocytic receptor inhibiting innate immune reactivity by extracellular
V-set domain recognition of sialic acid(Sia)-containing self-associated molecular patterns (SAMPs). We earlier showed
that V-set domain-deficientCD33-variant allele, protective against LOAD, is derived and specific to
hominin-lineage. We now report that CD33 also harbors multiple hominin-specific V-set domain mutations and explore selection forces that may have favored such
genomic changes. N-glycolylneuraminic acid (Neu5Gc), the preferred Sia-ligand of ancestral CD33 is absent in humans, due to hominin-specific, fixed
loss-of-function mutation in CMAH, which generates CMP-Neu5Gc from its
precursor,CMP-N-acetylneuraminic acid (Neu5Ac). Extensive mutational analysis and MD-simulations indicate
that fixed change in amino acid 21 of hominin V-set domain and conformational changes related to His45 corrected for Neu5Gc-loss by switching to
Neu5Ac-recognition. Considering immune-evasive molecular mimicry of SAMPs by pathogens, we found that
human-specific pathogens Neisseria gonorrhoeae and Group B Streptococcus (affecting fertility and fetuses/neonates respectively) selectively
bind huCD33 and this binding is significantly impacted by amino acid 21 modification. Alongside LOAD-protective CD33
alleles, humans harbor additional, derived, population-universal, cognition-protective variants absent in great ape genomes. Interestingly, 11 of 13
SNPs in these human genes (including CD33), that protect the cognitive health of elderly populations, are not shared by
genomes of archaic hominins: Neanderthals and Denisovans. Finally, we present a plausible evolutionary scenario to compile, correlate and comprehend existing
knowledge about huCD33 evolution and suggest that grandmothering emerged in humans.
Diet and gut microbiomes are intricately linked on both short and long timescales.
Changes in diet can alter the microbiome, while microbes in turn allow hosts to access novel diets. Bees are wasps that switched to a vegetarian lifestyle, and the
vast majority of bees feed on pollen and nectar.
Some stingless bee species, however, also collect carrion, and a few have fully reverted to a necrophagous lifestyle, relying on carrion for protein and forgoing flower visitation altogether. These “vulture” bees belong to the corbiculate apid clade, which is known for its ancient association
with a small group of core microbiome phylotypes.
Here, we investigate the vulture bee microbiome, along with closely related facultatively necrophagous and obligately pollinivorous species, to understand how
these diets interact with microbiome structure.
Via deep sequencing of the 16S rRNA gene and subsequent community analyses, we find that vulture bees have lost
some core microbes, retained others, and entered into novel associations with acidophilic microbes found in the environment and on carrion. The abundance of
acidophilic bacteria suggests that an acidic gut is important for vulture bee nutrition and health, as has been found in other carrion-feeding animals.
Facultatively necrophagous bees have more variable microbiomes than strictly pollinivorous bees, suggesting that bee diet may interact with microbiomes on both
short and long timescales.
Further study of vulture bees promises to provide rich insights into the role of the microbiome in extreme diet switches.
Throughout human evolutionary history, large-scale migrations have led to intermixing (ie. admixture) between previously separated human groups. While classical
and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains
underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the
selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations we show that this method
is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed
population. We apply this method to genome-wide SNP data of ~4,000 individuals in five admixed Latin American
cohorts from Brazil, Chile, Colombia, Mexico and Peru. Our approach replicates previous reports of selection in the HLA
region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many
of these signals with an alternative, commonly-used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect
responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals
inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes,
plausibly reflecting adaptations to novel dietary sources available in the Americas.
In all living organisms, genomic DNA continuously replicates by the proteins encoded in itself and undergoes
evolution through many generations of replication. This continuous replication coupled with gene expression and the resultant evolution are fundamental functions
of living things, but they have not previously been reconstituted in cell-free systems.
In this study, we combined an artificial DNA replication scheme with a reconstituted gene expression system and
microcompartmentalization to realize these functions. Circular DNA replicated through rolling-circle replication
followed by homologous recombinationcatalyzed by the proteins, phi29 DNA
polymerase, andCre recombinase expressed from the DNA. We encapsulated the system in microscale
water-in-oil droplets and performed serial dilution cycles. Isolated circular DNAs at Round 30 accumulated several
commonmutations, and the isolated DNA clones exhibited higher replicationabilities than the
original DNA due to its improved ability as a replication template, increased polymerase activity, and a reduced
inhibitory effect of polymerization by the recombinase.
The artificial genomic DNA, which continuously replicates using self-encoded proteins and autonomously improves
its sequence, provides a useful starting point for the development of more complex artificial cells.
[Keywords: DNA replication, cell-free synthetic biology, artificial cell, Darwinian
evolution]
Characterizing the natural selection of complex traits is important for
understanding human evolution and both biological and pathological mechanisms.
We leveraged genome-wide summary statistics for 870 polygenic traits and
attempted to quantify signals of selection on traits of different forms in European ancestry across 4 periods in human history and evolution.
We found that 88% of these traits underwent polygenic change in the past 2,000–3,000 years. Recent selection was associated with ancient selection signals in
the same trait. Traits related to pigmentation, body measurement and nutritional intake exhibited strong selection signals across different time scales. Our
findings are limited by our use of exclusively European data and the use of genome-wide association study data, which identify associations between genetic
variants and phenotypes that may not be causal.
In sum, we provide an overview of signals of selection on human polygenic traits and their characteristics across human evolution, based on a European subset of
human genetic diversity. These findings could serve as a foundation for further population and medical genetic studies.
…As shown in Figure 1, we focus on 2 primary goals. First, we describe the selection pressure on each trait at 4 different time scales
(Figures 2–5). This is achieved using various metrics derived from different statistical models (Mendelian randomization (MR), singleton density score, ancient genome analysis and so on),
each fitting a specific timeframe or form of selection. Second, we integrate these metrics to explore the association among selection pressures, trait
characteristics and functional genomic patterns (Figures 6–8), using linear regression and unsupervised clustering.
…Body measurements and contemporary reproductive success: Our analysis started by exploring natural selection pressure at the present time. We
hypothesized that the current natural selection of a trait is relevant to whether it could causally impact human reproductive success (that is, number of
offspring) and mating success (for this, we used the proxy of number of overall sexual partners). To quantify these causal effects, we applied MR on GWAS summary statistics between tested
traits and reproductive success, as well as between tested traits and mating success. At the statistical-significance cutoff of |zMR| > 4
(Methods), we found that 7.4% of traits with valid MR results (that is, traits passing sensitivity analysis) (40 out of 539) had a causal effect on the number of
offspring of males, whereas 5.9% (32 out of 542) of traits with valid MR results impacted the number of offspring of females (Supplementary
Table 2). Separating the traits into 15 categories (Figure 2A, Figure 2B), we observed that 52% (23⁄44) of
anthropometric body measurement traits such as height (zMR = 8.09, p = 3.33 × 10−16 in males; zMR =
4.91, p = 4.55 × 10−7 in females) were causally related to the number of offspring of males. By contrast, only 30% (14⁄47) of body measurement
traits were causally related to the number of offspring of females. In addition, the effect of another type of body measurement (dermatology traits such as skin
colour) on reproductive success also exhibited sex specificity: 38% (5⁄13) of dermatology traits influenced the number of offspring of males, but none affected the
number of offspring of females. However, when testing for 112 complex conditions such as schizophrenia11 and stroke15, polygenic risks showed
no statistically-significant causal effect on the numbers of offspring for
either males or females (nominal p > 0.05/112). The distribution of effect direction was also similar between disease and non-disease traits
(Fisher p = 0.40 for males, p = 0.71 for females).
For mating success (Supplementary
Figure 2), body measurement traits also had an impact: 44% of body measurement traits impacted the number of sexual partners of males, compared
with 12% affecting the number of sexual partners of females. Interestingly, among all 112 tested polygenic disease traits, schizophrenia (zMR =
7.37, p = 8.53 × 10−14) and attention-deficit hyperactivity disorder (zMR = 4.62, p = 1.92 × 10−6) increased the number of sexual
partners of males, in line with previous findings that increased genetic liability for schizophrenia does not confer a fitness advantage but does increase mating
success16. For males, the impact on
reproductive success of a trait was positively correlated with its impact on mating success (Supplementary Figure 2; Pearson correlation coefficient(PCC) 0.47, 95% CI 0.39 to 0.55,p = 9.30 × 10−31). However, this was not true for females, for whom the impact
on reproductive success of a trait was negatively correlated with its impact on mating success (Supplementary Figure 2; PCC −0.10, 95% CI −0.20 to 0,p = 0.02). This discrepancy is consistent with the evolutionary psychology theory that males and females adopt distinct sexual
strategies that shape assortative selection17.
Next, we investigated whether the trait impact on reproductive success and mating would differ between the sexes. In general, trait impact on human reproductive
success was similar for males and females (Figure 2c; PCC 0.38, 95% CI 0.32 to 0.44,p = 6.85 × 10−31). Trait impacts of mating success were also similar between the sexes (Supplementary Figure 2;
PCC 0.64, 95% CI 0.58 to 0.70,p = 9.18 × 10−106). Notably, high intelligence trait
statistically-significantly reduced the number of offspring in both females and males (zMR = −7.55, p = 2.18 × 10−14 in
females, zMR = −5.13, p = 1.45 × 10−7 in males), and increased the expected number of sexual partners for females
(zMR = 7.05, p = 8.97 × 10−13) (Supplementary Figure 1).
In addition, we applied causal analysis using summary effect estimates18
to all MR results to analyse the role of genetic correlation. We found that
most of the results were explained mainly by causal effects instead of genetic correlation. Using another GWAS19
dataset and applying MR bias estimation20, we again showed that our results were not explained by GWAS sample
overlap (‘MR analysis details’ in Supplementary Information).
Figure 2: Selection pressure in the present day and in recent history.A, B: Proportion of traits
showing MR causal effects on the number of offspring of males (a) and females (b) for each
category. c, Comparison of MR z scores between males (x-axis) and females (y-axis). Dashed lines indicate the statistical-significance threshold (|z| > 4). The text indicates selected traits with results of special
interest. DER, dermatology; NUT, nutrition; REP, reproduction; GI, gastrointestinal; PSY,
psychiatry; RES, respiratory; MED, medication; COG, social cognition; MUSC, musculoskeletal;
MET, metabolism; CIRC, circulation; NEU, neurology.
…Widespread polygenic adaptation in the past 2,000–3,000 years: At the statistical-significance threshold of p < (0.05/870 = 5.7
× 10−5), we found that 88% (761⁄870) of polygenic traits had a statistically-significant correlation between the GWASp-value and tSDS (ρSDS; Supplementary Table 3). Previous analysis has found that population stratification of UK Biobank might bias the estimated polygenic adaptation22.
Thus, to exclude this potential confound in our analyses, we applied another method with a different statistical model, which involves reconstructing the history
of polygenic scores(RHPS)23, based on RELATE24 (RHPS-RELATE, Methods). We set the reference panel as all European participants of 1000 Genomes to avoid population stratification. As shown in Supplementary
Table 3, the polygenic risk score (PRS) alteration in the past 100 generations (roughly equivalent to
2,800 years (ref. 24)) was mostly in accordance with ρSDS(PCC 0.25, 95%
CI 0.18 to 0.32,p = 3.96 × 10−13). Among 755 traits with statistically-significant non-zero ρSDS, 13.8% (104⁄755) showed a consistent statistically-significant alteration of PRS
(p for ‘Tx test’ from RHPS < 0.05/870, Methods), and 26.1% (197⁄755) showed a nominally
statistically-significant alteration (p for Tx test < 0.05). Notably, our RHPS-RELATE results also
highlighted those traits with the highest ρSDS, such as ease of skin tanning (p for ρSDS <10−100; p for Tx test
<10−100) and raw vegetable intake (p for ρSDS <10−100; p for Tx test
2.69 × 10−51) (Supplementary Table 3). In general, the results of RHPS-RELATE were
consistent with the ρSDS analysis, albeit at lower statistical power. Thus, we conclude that the ρSDS results are credible and can truly reflect
recent adaptation prevalence…by utilizing simulations of genetic drift and
demographic isolation strategies, our results suggest that population stratification did not drive a systematic bias on ρSDS. We consequently propose that the observed bias on height might not represent the majority of traits.
…When analysing all traits, we observed that dermatology traits generally showed the most statistically-significant selection signals (median
|ρSDS| = 0.69, Figure 3A, B), followed by nutrition intake (median |ρSDS| = 0.48; Supplementary Figure 4) and reproduction-related traits (median |ρSDS| = 0.30; Supplementary Figure 4). Ease of skin tanning was the trait with the most statistically-significant
adaptation (ρSDS = 0.96, p < 10−100; Figure 3c). Ever been drinkers
(ρSDS = −0.82, p < 10−100) and sitting height (ρSDS = 0.84, p < 10−100) were also among traits with an extreme adaptation signal (|ρSDS| > 0.8), which made up 3.3% of all traits (Supplementary Figure 4). Neurological traits such as brain
structures exhibited the least polygenic adaptation (median |ρ| = 0.05).
In contrast to non-disease traits, the adaptive pressure on polygenic disease traits was generally negative (median ρSDS = −0.08; permutation p = 3.22 × 10−6), especially for early-onset conditions such as autism spectrum disorder (median ρSDS =
−0.12; Supplementary Figure 5). The greatest evidence of negative adaptation was found for high cholesterol (ρSDS = −0.66, p < 10−100; Supplementary Figure 5). Still, we found evidence of positive
adaptation for a few diseases such as skin cancer and inflammatory bowel disease (ρSDS
> 0.2, p <10−100; Supplementary Figure 5), and even some early-onset conditions such as attention deficit hyperactivity
disorder (ρSDS = 0.20, p <2.16 × 10−24) and anorexia nervosa (ρSDS = 0.16, p =
1.24 × 10−19) (Supplementary Table 3). This result suggested that some of the disease traits might be by-products of other positive
selection events.
…As shown in Figure 4a and Supplementary Table 5, after controlling for covariances (for example, latitude, longitude and
genotyping coverage) and multiple tests, the polygenic burden of 78 traits was statistically-significantly associated with the percentage of hunter-gatherer
ancestry (HG%). By contrast, another 6 traits, such as denture usage, were associated with
time in at least one of 3 datasets. 7 of 13 dermatology traits were most predominantly associated with HG% (Figure 4a), with ‘ease of skin
tanning’ as the most statistically-significant example (regression tHG = 20.3, p = 1.74 × 10−38; Figure 4b). In the
Near East dataset, we observed that signals of selection on skin tanning varied by latitude (Figure 4c), with signals of positive selection
observed in regions of low latitude (latitude < 50°; t = 4.12, p = 1.91 × 10−5), but signals of negative selection observed at high latitudes (t = 4.95,
p = 3.80 × 10−7). After controlling for the impact of latitude, we observed a general ascending trend for ‘ease of skin tanning’ for the Near
East dataset, suggesting overall positive selection (regression tNear East = 5.81, p = 2.29 × 10−8; Figure
4c). We also found a nominally statistically-significant increment for ease of skin tanning in the pre-Neolithic period (regression tpre-Neolithic = 4.25, p = 1.11
× 10−5), but not in the Neolithic period (regression tNeolithic = 0.92, p = 0.18; Supplementary Figure
7).
Figure 3: Selection pressure in recent history.a, Distribution of absolute Spearman correlation (|ρSDS|) between the tSDS and GWASp-value for each category. The upper and lower margins of the box indicate the first and third quartiles of
ρSDS, and the thickened line its median. b,
ρSDS for all dermatology traits. The diagonal of the rhombus indicates
ρSDS, and the width its 95% CI, Scatter plotshowing the correlation between tSDS and
GWASp-value bin for the trait ‘ease of skin tanning’. Each point represents a bin of 1,000 SNPsranked by their
GWASp-value. The y-axis indicates the bin median tSDS.
Abbreviations as inFigure 2.
Figure 7: Population-average polygenic risk score trajectory for 765 traits. Trajectories are grouped into 4 clusters according to
their time-series similarity by hierarchical clustering. The y-axis shows the zscores of PRS.Colour marks different traits with overlapping trajectories, and dashed line marks median trajectory of each cluster.
…although all the above possibilities explained a proportion of disease heritability, there is still room for another ‘trivial explanation’: natural selection
was indeed eliminating the risk alleles but simply not fast enough, due to the small effect of each allele and the small effective population size at the risk loci8,46
The mosaic brain evolution hypothesis, stating that brain regions can evolve
relatively independently during cognitive evolution, is an important idea to understand how brains evolve with potential implications even for human brain
evolution.
Here, we provide the first experimental evidence for this hypothesis through an artificial selection experiment in the guppy (Poecilia reticulata).
After 4 generations of selection on relative telencephalon volume (relative to
brain size), we found substantial changes in telencephalon size but no changes in other regions. Further comparisons revealed that up-selected lines had larger
telencephalon, while down-selected lines had smaller telencephalon than wild Trinidadian populations.
Our results support that independent evolutionary changes in specific brain regions through mosaic brain evolution can be important facilitators of cognitive
evolution…The rate of evolution shown here is similar to that seen when brain size was the target of selection (24); a 9% difference in brain mass between the
large-brain and small-brain lines was found after 2 generations of artificial selection and a 15% difference after 5 generations of selection (50). In contrast to
the aforementioned artificial selection experiment on relative brain size in guppies, which found a clear reduction in fecundity (ie. lower offspring number) in
the large-brain lines (24), we did not find any evidence for any reproductive trade-off with telencephalon size
The use of spoken and written language is a capacity that is unique to humans. Individual differences in reading-related and language-related skills are
influenced by genetic variation, with twin-based heritability estimates of 30–80%, depending on the trait. The relevant genetic architecture is complex,
heterogeneous, and multifactorial, and yet to be investigated with well-powered studies.
Here, we present a multi-cohort genome-wide association study (GWAS) of 5 traits assessed individually using
psychometric measures: word reading, non-word reading, spelling, phoneme awareness, and non-word repetition, with total sample sizes ranging from 13,633 to 33,959
participants aged 5–26 years (12,411 to 27,180 for those with European ancestry, defined by principal component analyses).
We identified a genome-wide statistically-significant association with word reading (rs11208009, p = 1.098 x 10–8) independent of known loci associated
with intelligence or educational attainment. All five reading/language-related traits had robust SNP-heritability
estimates (0.13–0.26), and genetic correlations between them were modest to high. Using genomic structural equation modelling, we found evidence for a
shared genetic factor explaining the majority of variation in word and non-word reading, spelling, and phoneme awareness, which only partially overlapped with
genetic variation contributing to non-word repetition, intelligence and educational attainment.
A multivariate GWAS was performed to jointly analyse word and non-word reading, spelling, and phoneme
awareness, maximizing power for follow-up investigation. Genetic correlation analysis of multivariate GWAS results with
neuroimaging traits identified association with cortical surface area of the banks of the left superior temporal sulcus, a brain region with known links to
processing of spoken and written language.
Analysis of evolutionary annotations on the lineage that led to modern humans showed enriched heritability in regions depleted of Neanderthal variants.
Together, these results provide new avenues for deciphering the biological underpinnings of these uniquely human traits.
Haldane9s Dilemma refers to the concern that the need for many “selective deaths” to complete a substitution creates a speed limit to adaptation. However,
discussion of this concern has been marked by confusion over which features of substitutions produce limits to the speed of adaptation, what those limits are, and
the consequences of violating speed limits. The term 9substitution load9 has been particularly unhelpful in this regard. Here we distinguish different lines of
reasoning that lead to speed limits, including one line of reasoning which has not yet been fully addressed. We then apply these lines of reasoning to a dataset
measuring survival and fecundity of 517 different genotypes of Arabidopsis thaliana grown in eight different environmental conditions. We estimate highly
permissive limits to the speed of adaptation in all environmental conditions. We also estimate that much higher proportions of deaths contribute to adaptation than
were anticipated during historical discussions of speed limits.
Food-caching birds use spatial cognition to recover food stores
and survive winter
Variation in cognitive phenotypes is associated with variation across the genome
Top outlier genes are associated with hippocampal development and function
Results link cognitive and genetic variation, making it available for selection
Spatial cognition is used by most organisms to navigate their environment. Some species rely particularly heavily on specialized spatial cognition to survive,
suggesting that a heritable component of cognition may be under natural selection. This idea remains largely untested outside of humans, perhaps because cognition in
general is known to be strongly affected by learning and experience.
We investigated the genetic basis of individual variation in spatial cognition used by non-migratory food-caching birds to recover food stores and survive harsh
montane winters.
Comparing the genomes of wild, free-living birds ranging from best to worst in their performance on a spatial cognitive task revealed statistically-significant associations
with genes involved in neuron growth and development and hippocampal function.
These results identify candidate genes associated with differences in spatial cognition and provide a critical link connecting individual variation in spatial
cognition with natural selection.
…We used whole-genome sequencing, combining traditional genome-wide association studies(GWASs) and aRandom Forest machine learning approach, to compare
the genomes of wild, free-living birds. We sampled birds from high and low elevations that performed the best on a spatial cognitive task, all of whom survived
more than one year (n = 22), to those that performed the worst on the task and generally did not survive more than 1 year (n = 15⁄20)—the group
with better spatial cognition was associated with a statistically-significant survival advantage (Fisher’s exact test, p < 0.001). Birds from both high
and low elevations were selected for each performance group to ensure that the strongest signal between groups was variation in cognition and not a correlate of
elevation…We sampled 42 mountain chickadees across 3 years of testing from the
extremes of the cognitive performance range: 22 were chosen as the best and 20 were chosen as the worst. Performance scores of individuals in the best and worst
groups did not overlap, but individual variation within each group provided a continuous distribution from best to worst (Figure 1F). We
intentionally chose individuals with means in the tails of the cognitive performance distribution (Figures 1E and 1F) to
amplify the signal of genetic associations, although we acknowledge that this design could inflate associations from loci with the largest effect to the detriment
of small-effect polygenes. There was a statistically-significant difference in the mean number of errors per trial between
best (mean errors/trial: 0.16 ± 0.045) and worst (0.60 ± 0.05) performers (cognitive category [best versus worst]: F1,38 = 72.91, p <
0.0001; Figure 1F), but there was not a statistically-significant effect of elevation, as we selectively picked the best and worst performers
at each elevation (elevation [high versus low]: F1,38 = 1.38, p = 0.247; total trials completed [covariate]: F1,38 = 5.26,
p = 0.028).
Parrots are well-known for their exceptionally long lives and cognitive complexity. While previous studies have demonstrated a correlation between longevity and
brain size in a variety of taxa, little research has been devoted to understanding this link in parrots. Here we employed a large-scale comparative analysis that
investigated the influence of brain size and life history variables on patterns of longevity. Specifically, we addressed two hypotheses for evolutionary drivers of
longevity: the Cognitive Buffer Hypothesis, which proposes that increased cognitive abilities enable longer life spans, and the Expensive Brain Hypothesis, which
holds that the increase in life span is caused by prolonged developmental time of and increased parental investment in, large brained offspring. We estimated life
expectancy from detailed zoo records for 133,818 individuals across 244 parrot species. Using Bayesian structural equation models, we found a consistent
correlation between relative brain size and life expectancy in parrots. This correlation was best explained by a direct effect of relative brain size. Notably, we
found no effects of developmental time, clutch size, or age at first reproduction. Our results provide support for the Cognitive Buffer Hypothesis, and demonstrate
a principled Bayesian approach that addresses data
uncertainty and imputation of missing values.
The admixture between modern humans and Neandertals has resulted in ~2% of the genomes of present-day non-Africans still being composed of Neanderthal
DNA. Association studies have shown that introgressedDNA still significantly
influences skin and hair traits, immunity and behavioral phenotypes in people today. Several of the phenotype-associated archaic variants had links to
regulatory effects as well. In general, analyses of allele-specific expression, regulatory sequence composition and cis-eQTL have demonstrated asignificant contribution of this introgressed DNA to the
transcriptomic landscape in people today. However, little is known about the impact of Neanderthal DNA on
trans-eQTLs—long-range regulatory effects that have been shown to explain ~20% of expression variation.
Here, we used blood eQTL results from >30,000 individuals fromeQTLGen Consortium. The cohort size allowed for a robustidentification of trans-eQTLs and
in addition enabled quantifying the role of transcription factors (TF) in mediating long-range regulatory effects. In our study we used this information to
(1) annotate trans-eQTLs that are linked to Neanderthal variants and (2) predictlong-range regulatory
effects that are induced by Neanderthal DNA byscreening for the predicted target genes of TFs that are
cis-eQTLs linked to Neanderthal variants. We show that both trans-eQTL-associated Neanderthal variants and those predicted to have long-range regulatory effects affect genes in genomic regions devoid
of Neanderthal DNA. In addition, both types of variants included candidates for local adaptation and show
associations with autoimmune disorders, a severe COVID-19 phenotype, blood cell type composition and
anthropometric measures.
Our results suggest that the regulatory reach of Neanderthal DNA goes beyond the 40% of genomic sequence that it
still covers in present-day non-Africans and that via this mechanism Neanderthal DNA additionally influences the
phenotypic variation in people today.
There has been extensive research on the ecology and evolution of social life in animals that live in groups. Less attention, however, has been devoted to
apparently solitary species, even though recent research indicates that they also possess complex social behaviors.
To address this knowledge gap, we artificially selected on sociability, defined as the tendency to engage in nonaggressive activities with others, in fruit
flies. Our goal was to quantify the factors that determine the level of sociability and the traits correlated with this feature.
After 25 generations of selection, the high-sociability lineages showed sociability scores about 50% higher than did the low-sociability lineages.
Experiments using the evolved lineages indicated that there were no differences in mating success between flies from the low and high lineages. Both males and
females from the low lineages, however, were more aggressive than males and females from the high lineages. Finally, the evolved lineages maintained their
sociability scores after 10 generations of relaxed selection, suggesting no costs to maintaining low and high sociability, at least under our settings.
Sociability is a complex trait, which we currently assess through genomic work on the evolved lineages.
…Field and laboratory studies indicate that both larval and adult fruit flies show statistically-significant sociability, as they prefer to group together at food patches (Durisko et al 2014;
Anderson et al 2016; Scott et al 2018; Dukas 2020). In the adults, the broad sense heritability of sociability is about 0.22
(Scott et al 2018). The heritable variation in sociability opens up exciting opportunities for assessing the evolutionary biology of this trait in a
prominent model animal.
…Methods: …We derived all artificial selection lineages from a population of ~600 wild Drosophila melanogaster females caught in various
locations in and around Hamilton, Ontario in late spring and early summer 2018…We mixed 3 F1 males and 3 F1 females from each of these isofemale lines together in
3 large populations. We then amplified these populations over one or 2 generations, generating a large total population size of ~6,000 flies, mixed among the three
populations, and then randomly assigned flies to 12 separate lineages: 4 lineages to be selected for low sociability, 4 lineages to be selected for high
sociability, and 4 control lab adaptation and domestication lineages
…We developed a novel arena capable of both quantifying the sociability of groups of flies and allowing for the selection of flies based on their sociability
(Figure 1A).
Figure 1: The arena used for quantification of and artificial selection on sociability. (A) The
arena without the lid, showing the 8 compartments and an example arrangement of 16 flies. (B) The arena with the lid (note that
the lid and swinging door were fully transparent, and opacity in the diagram is only for clarity). A foam plug at the central hole (not shown in the figure)
allowed fly movement among the 8 compartments when at the top position, and locked flies within their compartment when in the bottom position.
Overview Of Artificial Selection Methods: Overall, each generation, we tested 12 groups of 16 males and 12 groups of 16 females from each of
the 8 selection lineages (four low sociability, 4 high sociability). We selected 4 flies from each group of 16 flies to produce the next generation. In tests
involving the low-sociability lineages, we chose the least sociable flies. In tests involving the high-sociability lineages, we chose the most sociable flies (see
detailed methods below). We ran 2 experimental sessions per day over 2 days, with each session including 3 male groups and 3 female groups from each of the 8
lineages…At 1230h, we blocked the central area of each arena by pushing down the foam plug, sealing the flies into the compartment that they had settled in.
At this point, we recorded the number of flies in each compartment of each arena. We then selected flies to produce the next generation for each lineage based on
the number of flies in each compartment. We removed flies by rotating the lid so that the off-center hole was above a particular compartment, then rotating the
plastic door so that the hole was uncovered, and aspirating the flies out. For the low-sociability lineages, we selected four flies per arena from compartments
with the lowest numbers of flies, unless those numbers were 3 or more, in which case we took flies from other replicate arenas of that session with smaller groups.
Similarly, for the high-sociability lineages, we selected 4 flies per arena from the compartment(s) with the highest number of flies, unless that number was 3 or
less, in which case we took flies from larger groups in replicate arenas. The unselected flies from each arena were discarded. After each of the 4 selection
sessions, we ended with 12 males and 12 females selected per lineage. We then placed the selected flies in sex-specific holding vials.
Figure 2: Divergence in selection treatments in sociability score over 25 generations. Mean ± SEM sociability scores across all selection lineages for low-sociability and high-sociability treatments in (A) females and (B) males. The same data are displayed by replicate lineages (error bars excluded for clarity)
in (C) females and (D) males. Values statistically-significantly above 1 (dashed lines) indicate
statistically-significant sociability.
Figure 4: Aggression frequency in (A) females and (B) males from the
selection treatments after 25 generations of selection. Inner box plots show median, interquartile range(IQR), and whiskers up to 1.5 × IQR. Outer violin plots show the shape of the distribution of the data.
Convolutional Neural Networks (CNNs) can perform similarly or better than standard genomic prediction methods
when sufficient genetic, environmental, and management data are provided.
Predicting phenotypes from genetic (G), environmental (E), and management (M) conditions is a long-standing challenge with implications to agriculture,
medicine, and conservation. Most methods reduce the factors in a dataset (feature engineering) in a subjective and potentially oversimplified manner. Deep neural
networks such as Multilayer Perceptrons (MPL) and Convolutional Neural Networks (CNN) can
overcome this by allowing the data itself to determine which factors are most important. CNN models were
developed for predicting agronomic yield from a combination of replicated trials and historical yield survey data. The results were more accurate than standard
methods when tested on held-out G, E, and M data (r = 0.50 vs. r = 0.43), and performed slightly worse than standard methods when only G was
held out (r = 0.74 vs. r = 0.80). Pre-training on historical data increased accuracy compared to trial data alone. Saliency map analysis
indicated the CNN has “learned” to prioritize many factors of known agricultural importance.
Human same-sex sexual behaviour (SSB) is heritable, confers no immediately obvious direct reproductive or
survival benefit and can divert mating effort from reproductive opportunities. This presents a Darwinian paradox: why has SSB been maintained despite apparent selection against it?
We show that genetic effects associated with SSB may, in individualswho only engage in opposite-sex
sexual behaviour (OSB individuals), confer a mating advantage.
Using results from a recent genome-wide association study of SSB and a new genome-wide association study on
number of opposite-sex sexual partners in 358,426 individuals, we show that, among OSB individuals,genetic
effects associated with SSB are associated with having more opposite-sex sexual partners. Computer simulations suggest
that such a mating advantage for alleles associated with SSB could help explain how it has been evolutionarily
maintained.
Caveats include the cultural specificity of our UK and US samples, the societal regulation of sexual behaviour in these populations, the difficulty of measuring
mating success and the fact that measured variants capture a minority of the total genetic variation in the traits.
Following domestication in the lower Yangtze River valley 9,400 years ago, rice farming spread throughout China and changed lifestyle patterns among Neolithic
populations. Here, we report evidence that the advent of rice domestication and cultivation may have shaped humans not only culturally but also genetically.
Leveraging recent findings from molecular genetics, we construct a number of polygenic scores(PGSs) of behavioural traits and examine their associations with rice
cultivation based on a sample of 4,101 individuals recently collected from mainland China. A total of 9 polygenic traits and genotypes are investigated in
this study, including PGSs of height,body
mass index, depression, time discounting, reproduction, educational attainment, risk preference, ADH1B rs1229984 and ALDH2 rs671.
Two-stage least-squares estimates of the county-level percentage of cultivated land devoted to paddy rice on the PGS
of age at first birth (b = −0.029, p = 0.021) and ALDH2 rs671 (b = 0.182, p
< 0.001) are both statistically-significant and robust to a wide range
of potential confounds and alternative explanations.
These findings imply that rice farming may influence human evolution in relatively recent human history.
Animal hosts have initiated myriad symbiotic associations with microorganisms and often have maintained these symbioses for millions of years, spanning drastic
changes in ecological conditions and lifestyles. The establishment and persistence of these relationships require genetic innovations on the parts of both
symbionts and hosts.
The nature of symbiont innovations depends on their genetic population structure, categorized here as ‘open’, ‘closed’ or ‘mixed’. These categories reflect
modes of inter-host transmission that result in distinct genomic features, or genomic syndromes, in symbionts. Although less studied, hosts also innovate in order
to preserve and control symbiotic partnerships.
New capabilities to sequence host-associated microbial communities and to experimentally manipulate both hosts and symbionts are providing unprecedented
insights into how genetic innovations arise under different symbiont population structures and how these innovations function to support symbiotic
relationships.
Manifold and diverse applications of doubled haploid (DH)
plants have emerged in academy and in the plant breeding industry since the first discovery of a haploid mutant in the Jimson Weed (Datura
stramonium), followed by the first reports about anther culture in the same species, maternal haploids by wide crosses in tobacco (Nicotiana tabacum L.) and barley (Hordeum vulgare L.), interspecific hybridization, ovary culture (gynogenesis), isolated microspore culture, and more recently the CENH3 approach in thale cress
(Arabidopsis thaliana L.) and other species. Research
and development efforts were and are still substantial in both user groups.
Luckily, often academic and industrial partners cooperate in challenging and sometimes voluminous projects worldwide. Not only to develop innovative DH
protocols and technologies per se, but also to exploit the advantages of DH plants in a huge variety of research and development experiments. This review
concentrates not on the DH technologies per se, but on the application of DHs in plant-related research and development projects.
…While the primary application of DHs was to fix genetic variability as fast as possible by immediately reaching full homozygosity (one “step” versus several
selfing generations), this advantage of DHs was later and is still widely used in marker-assisted selection in academy. Later, with the development of cheaper and
easier molecular biological and genomic tools and technologies, the link between DHs and marker applications in commercial breeding programs was accelerated as
well.
Today, DHs in many plant species are routinely used, often combined with diverse tool kits from the fields of genomics, transgenics (e.g. reverse breeding), bioinformatics, tissue culture, genome editing, epigenetics, but phenotyping and sophisticated
field nursery technologies as well. This is often possible in species in which the efficiency of DH production was improved by optimization of several steps, being
it either in vitro or in vivo. Those improvements (described in other chapters of this book) led mainly to accelerated in vitro haploid cell induction, better
quality and quantity of organogenesis and regeneration, in vivo haploid induction, and genome doubling.
…This review article here starts with the use of DHs to analyze their genetics and agronomic characters and the comparison of DH populations with conventionally
generated (selfed) populations under field conditions. In the following sections, the use of DHs in diverse genetic mapping studies and gene cloning approaches
(and other genomic applications) is described, as well as their use in breeding and research of transgenic plants. The most recent reports from large
biostatistical projects, genome editing, and phenotyping applications are mentioned too.
In particular, the following applications of DHs in plant breeding and applied research will be discussed:
Recombination and fixation of genetic variance
Use of haploid and DH technologies to develop wide crosses and use of hybridization
DHs for mapping and diverse range of MAS procedures and strategies
DHs for genomic selection and genomic prediction
Haploid tissues used for genetic transformation and development of stable transgenic lines and DHs for breeding with transgenic lines
Use of haploid cells and tissues for increasing genetic variation by mutation
The possession of permanent, adipose breasts in women is a uniquely human trait that develops during puberty, well in advance of the first pregnancy. The
adaptive role and developmental pattern of this breast morphology, unusual among primates, remains an unresolved conundrum. The evolutionary origins of this trait
have been the focus of many hypotheses, which variously suggest that breasts are a product of sexual selection or of natural selection due to
their putative role in assisting in nursing or as a thermoregulatory organ. Alternative hypotheses assume that permanent breasts are a by-product of other
evolutionary changes.
We review and evaluate these hypotheses in the light of recent literature on breast morphology, physiology, phylogeny, ontogeny, sex differences, and genetics
in order to highlight their strengths and flaws and to propose a coherent perspective and a new hypothesis on the evolutionary origins of perennially enlarged
breasts in women.
We propose that breasts appeared as early as Homo ergaster,
originally as a by-product of other coincident evolutionary processes of adaptive importance. These included an increase in subcutaneous fat tissue
(SFT) in response to the demands of thermoregulatory and energy storage, and of the ontogenetic development of the
evolving brain. An increase in SFT triggered an increase inoestradiol levels (E2). An
increase in meat in the diet of early Homo allowed for further hormonal changes, such as greater dehydroepiandrosterone(DHEA/S)
synthesis, which were crucial for brain evolution. DHEA/S is also easily converted to E2 in E2-sensitive body parts, such as breasts and gluteofemoral regions, causing fat
accumulation in these regions, enabling the evolution of perennially enlarged breasts.
Furthermore, it is also plausible that after enlarged breasts appeared, they were co-opted for other functions, such as attracting mates and indicating
biological condition.
Finally, we argue that the multifold adaptive benefits of SFT increase and hormonal changes outweighed the
possible costs of perennially enlarged breasts, enabling their further development.
Companies have recently begun to sell a new service to patients considering in vitro fertilization: embryo selection based on polygenic scores
(ESPS). These scores represent individualized predictions of health and other outcomes derived from genome-wide
association studies in adults to partially predict these outcomes.
This article includes a discussion of many factors that lower the predictive power of polygenic scores in the context of embryo selection and quantifies these
effects for a variety of clinical and nonclinical traits. Also discussed are potential unintended consequences of ESPS
(including selecting for adverse traits, altering population demographics, exacerbating inequalities in society, and devaluing certain traits).
Recommendations for the responsible communication about ESPS by practitioners are provided, and a call for a
society-wide conversation about this technology is made.
…Recommendations For Responsible Communication Of Expected Gains From ESPS:
Emphasize absolute, not relative, risk reduction.
Patients have reported greater intention to accept interventions,32 and health care professionals have reported greater willingness to
purchase,33 prescribe,34,35 and view interventions as therapeutically effective,35,36 when the benefits are presented in terms of
relative rather than absolute risk reduction. Given this consistent trend in the literature,37,38 absolute risk reduction should be the most salient
measure of expected gain in tables, figures, and other materials.39,40 Relative risk reduction associated with embryo selection based on
polygenic scores (ESPS) should never be presented in isolation.41
Provide phenotype-specific estimates of expected gains.
In the phenotypes we assessed, expected gains from ESPS differed widely—from an absolute risk reduction of
0.12% to 8.5% and a relative risk reduction of 15% to 80% in persons of European ancestries. Companies should provide expected estimates of gain for each
phenotype for which screening is offered as well as for the screening of multiple phenotypes at once. Expected gains from select phenotypes should not be
offered as examples from which consumers and clinicians might improperly generalize.41 Further, consumers should be aware that “expected gains” for
phenotypes that are defined by clinical cutoff points may not be practically meaningful.
Provide ancestry-specific estimates of expected gains.
Currently, ESPS is not nearly as effective for consumers with non-European ancestries. Both the expected
gains for each ancestral group and the uncertain gains for those of multiple ancestries should be prominently acknowledged, in plain language. Technical
statements buried in fine print, such as “in demographics different from the Caucasian training set, sensitivity will be reduced”,42 are
inadequate.
Provide risk-specific estimates of expected gains.
Expected gains will differ depending on the lifetime risk of the phenotype in the embryo “population.” This risk, in turn, will depend on family history and
on the environment in which the resulting child is expected to be reared.
Emphasize that expected gains (and risks) are uncertain.
Companies should make clear that ESPS predictions have very wide prediction intervals that sometimes cross
zero and that pleiotropy presents both risks and uncertainties regarding the other traits that do or might correlate with those the parent is selecting.
Avoid exaggerating the benefits of screening additional embryos.
Claims such as “the more sibling embryos you have to choose from, the greater the relative reduction in risk”41 are misleading. Even for
cases in which the expected gains of ESPS increase largely with each additional embryo for the first 5 embryos, the
incremental gains will be smaller with each of the next 5 additional embryos and will slow dramatically thereafter.11 This caution will be
especially important if progress in stem-cell technologies makes it possible to create sperm or egg cells from a person’s blood or skin cells, yielding many
more embryos, noninvasively, than is possible today.43,44
The magnitude of human sex differences varies across contexts.
An evolutionarily informed model of these environmental influences is discussed.
Many sex differences are largest under optimal conditions and shrink as conditions deteriorate.
Human sex differences in growth, social behavior, and cognition illustrate the approach.
The approach has implications for better understanding sex-specific vulnerabilities.
The contributions of evolutionary processes to human sex differences are vigorously debated. One counterargument is that the magnitude of many sex differences
fluctuates from one context to the next, implying an environment origin. Sexual
selection provides a framework for integrating evolutionary processes and environmental influences on the origin and magnitude of sex differences.
The dynamics of sexual selection involve competition for mates and discriminative mate choices. The associated traits are typically exaggerated and
condition-dependent, that is, their development and expression are very sensitive to social and ecological conditions. The magnitude of sex differences in sexually
selected traits should then be largest under optimal social and ecological conditions and shrink as conditions deteriorate.
The basics of this framework are described, and its utility is illustrated with discussion of fluctuations in the magnitude of human physical, behavioral, and
cognitive sex differences.
[Keywords: sex differences, sexual selection, cognition, condition-dependent, stressor]
The Modern Synthesis (or “Neo-Darwinism”), which arose out of the reconciliation
of Darwin’s theory of natural selection and Mendel’s research on genetics, remains the foundation of evolutionary theory. However, since its inception, it has been
a lightning rod for criticism, which has ranged from minor quibbles to complete dismissal.
Among the most famous of the critics was Stephen Jay Gould, who, in
1980, proclaimed that the Modern Synthesis was “effectively dead.” Gould and others claimed that the action of natural selection on random mutations was
insufficient on its own to explain patterns of macroevolutionary diversity and divergence, and that new processes were required to explain findings from the fossil
record. In 1982, Charlesworth, Lande, &
Slatkin published a response to this critique in Evolution, in which they argued that Neo-Darwinism was indeed sufficient to explain macroevolutionary
patterns.
In this ‘Perspective’ for the 75th Anniversary of the Society for the Study of Evolution, we review Charlesworth et al in its historical context
and provide modern support for their arguments. We emphasize the importance of microevolutionary processes in the study of macroevolutionary patterns.
Ultimately, we conclude that punctuated equilibrium did not represent a major revolution in evolutionary biology—although debate on this point stimulated
important research and furthered the field—and that Neo-Darwinism is alive and well.
[Keywords: evolutionary theory, Gould, macroevolution, microevolution, punctuated equilibrium, species selection]
A geographical gradient of height has existed in Japan for approximately 100 years. People in northern Japan tend to be taller than those in southern Japan. The
differences in annual temperature and day length between the northern and southern prefectures of Japan have been suggested as possible causes of the height
gradient. Although height is well known to be a polygenic trait with high heritability, the genetic contributions to the gradient have not yet been explored.
Polygenic score (PS) is calculated by aggregating the effects of genetic
variants identified by genome-wide association studies(GWASs) to predict the traits of individual subjects. Here, we calculated the PS of height for 10,840 Japanese
individuals from all 47 prefectures in Japan.
The median height PS for each prefecture was statistically-significantly correlated with the mean height of females and males obtained from another independent
Japanese nation-wide height dataset, suggesting genetic contribution to the observed height gradient. We also found that individuals and prefectures genetically
closer to continental East Asian ancestry tended to have a higher PS; modern Japanese people are considered to have originated as result of admixture between
indigenous Jomon people and immigrants from continental East Asia.
Another PS analysis based on the GWAS using only the mainland Japanese was conducted to evaluate the effect of
population stratification on PS. The result also
supported genetic contribution to height, and indicated that the PS might be affected by a bias due to population stratification even in a relatively homogenous
population like Japanese.
Bones and teeth are important sources of Pleistocene hominin DNA, butare rarely recovered at
archaeological sites. Mitochondrial DNA has been retrieved from cave sediments, but provides limited value for studying
population relationships.
We therefore developed methods for the enrichment and analysis of nuclear DNA from sediments, and applied them to cave
deposits in western Europe and southern Siberia dated to between approximately 200,000 and 50,000 years ago.
We detect a population replacement in northern Spain approximately 100,000 years ago, accompanied by a turnover of mitochondrial DNA. We also identify 2 radiation events in Neanderthal history during the early part of the Late Pleistocene.
Our work lays the ground for studying the population history of ancient hominins from trace amounts of nuclear DNA in
sediments.
Phenotype prediction is a key goal for medical genetics. Unfortunately, most genome-wide association studies are done in European populations, which reduces the
accuracy of predictions via polygenic scores in non-European populations. Here, we use population genetic models to show that human demographic history and
negative selection on complex traits can result in population-specific genetic architectures.
For traits where alleles with the largest effect on the trait are under the strongest negative selection, approximately half of the heritability can be
accounted for by variants in Europe that are absent from Africa, leading to poor performance in phenotype prediction across these populations. Further, under such
a model, individuals in the tails of the genetic risk distribution may not be identified via polygenic scores generated in another population. We empirically test
these predictions by building a model to stratify heritability between European-specific and shared variants and applied it to 37 traits and diseases in the UK
Biobank. Across these phenotypes, ~30% of the heritability comes from European-specific variants.
We conclude that genetic association studies need to include more diverse populations to enable the utility of phenotype prediction in all populations.
[Keywords: negative selection, complex traits, polygenic scores, risk prediction, population history, population genetics, simulations]
Temporal genomic data hold great potential for studying evolutionary processes such as speciation. However, sampling across speciation events would, in many
cases, require genomic time series that stretch well back into the Early Pleistocene sub-epoch. Although theoretical models suggest that DNAshould survive on this timescale, the
oldest genomic data recovered so far are from a horse specimen
dated to 780–560 thousand years ago.
Here we report the recovery of genome-wide data from three mammoth specimens dating to the Early and Middle Pleistocene sub-epochs, two of which are more than
one million years old. We find that two distinct mammoth lineages were present in eastern Siberia during the Early Pleistocene. One of these lineages gave rise to
the woolly mammoth and the other represents a previously unrecognized lineage that was ancestral to the first mammoths to colonize North America. Our analyses
reveal that the Columbian mammoth of North America traces its ancestry to a Middle Pleistocene hybridization between these two lineages, with roughly equal
admixture proportions. Finally, we show that the majority of protein-coding changes associated with cold adaptation in woolly mammoths were already present one
million years ago.
These findings highlight the potential of deep-time palaeogenomics to expand our understanding of speciation and long-term adaptive evolution.
This is a comparative study attempting to explain the pattern of cooperation across a number of microbial species. Hamilton’s inclusive-fitness theory makes the very general prediction that increased genetic
relatedness should drive the evolution of cooperation. Various arguments have dismissed the validity of this prediction in microbes, but without ever testing the
broad taxonomic support for those arguments. Here, we rehabilitate the central role of relatedness by showing that its power to predict cooperative gene content
holds across the full diversity of the human gut microbiota. Explaining broad-scale patterns is critical to a unifying variable for predictive science and broad
applications. The manipulation of relatedness may offer an opportunity to engineering microbial communities, such as the gut microbiota.
Through the secretion of “public goods” molecules, microbes cooperatively
exploit their habitat. This is known as a major driver of the functioning of microbial communities, including in human disease. Understanding why microbial species
cooperate is therefore crucial to achieve successful microbial community management, such as microbiome manipulation.
A leading explanation is that of Hamilton’s inclusive-fitness framework. A cooperator can indirectly transmit its genes by helping the reproduction of an
individual carrying similar genes. Therefore, all else being equal, as relatedness among individuals increases, so should cooperation. However, the predictive
power of relatedness, particularly in microbes, is surrounded by controversy.
Using phylogenetic comparative analyses across the full diversity of the human gut microbiota and six forms of cooperation, we find that relatedness is
predictive of the cooperative gene content evolution in gut-microbe genomes. Hence, relatedness is predictive of cooperation over broad microbial taxonomic levels
that encompass variation in other life-history and ecology details.
This supports the generality of Hamilton’s central insights and the relevance of relatedness as a key parameter of interest to advance microbial predictive and
engineering science.
Objectives: Debate about the cause of IQ score gaps between Black and White populations has persisted within genetics, anthropology, and
psychology. Recently, authors claimed polygenic scores provide evidence that a substantial portion of differences in cognitive performance between Black and White
populations are caused by genetic differences due to natural selection, the “hereditarian hypothesis.” This study aims to show conceptual and methodological flaws
of past studies supporting the hereditarian hypothesis.
Materials and methods: Polygenic scores for educational attainment were constructed for African and European samples of the 1000 Genomes
Project. Evidence for selection was evaluated using an excess variance test. Education associated variants were further evaluated for signals of selection by
testing for excess genetic differentiation (Fst). Expected mean difference in IQ for populations was calculated under a neutral evolutionary scenario
and contrasted to hereditarian claims.
Results: Tests for selection using polygenic scores failed to find evidence of natural selection when the less biased within-family
GWAS effect sizes were used. Tests for selection using Fst values did not find evidence of natural selection.
Expected mean difference in IQ was substantially smaller than postulated by hereditarians, even under unrealistic assumptions that overestimate genetic
contribution.
Conclusion: Given these results, hereditarian claims are not supported in the least. Cognitive performance does not appear to have been under
diversifying selection in Europeans and Africans. In the absence of diversifying selection, the best case estimate for genetic contributions to group differences
in cognitive performance is substantially smaller than hereditarians claim and is consistent with genetic differences contributing little to the Black-White
gap.
Extensive allelic variation in agronomically important genes serves as the basis of rice breeding. Here, we present a comprehensive map of rice
quantitative trait nucleotides (QTNs) and inferred QTN effects based on 8
genome-wide association study cohorts. Population genetic analyses revealed that domestication, local adaptation and heterosis are all associated with
QTN allele frequency changes. A genomenavigation system, RiceNavi, was developed for QTN pyramiding and breeding route optimization, and implemented in the improvement of a widely cultivated indica variety.
This work presents an efficient platform that bridges ever-increasing genomic knowledge and diverse improvement needs in rice.
The deep evolutionary history of African populations, since the emergence of modern humans more than 300,000 years ago, has resulted in high genetic diversity
and considerable population structure. Selected genetic variants have increased in frequency due to environmental adaptation, but recent exposures to novel
pathogens and changes in lifestyle render some of them with properties leading to present health liabilities. The unique discoverability potential from African
genomic studies promises invaluable contributions to understanding the genomic and molecular basis of health and disease. Globally, African populations are
understudied, and precision medicine approaches are largely based on data from European and Asian-ancestry populations, which limits the transferability of
findings to the continent of Africa. Africa needs innovative precision medicine solutions based on African data that use knowledge and implementation strategies
aligned to its climatic, cultural, economic and genomic diversity.
2021-lenton.pdf: “Survival of the Systems”, Timothy M. Lenton, Timothy A. Kohler,
Pablo A. Marquet, Richard A. Boyle, Michel Crucifix, David M. Wilkinson, et al (2021-01-04; backlinks):
Highlights:
Recent theoretical progress highlights that natural selection can occur based solely on differential persistence of biological entities, without the need for
conventional replication.
This calls for a reconsideration of how ecosystems and social (-ecological) systems can evolve, based on identifying system-level properties that affect
their persistence.
Feedback cycles have irreducible properties arising from the interactions of unrelated components, and are critical to determining ecosystem and social
system persistence.
Self-perpetuating feedbacks involving the acquisition and recycling of resources, alteration of local environmental conditions, and amplification of
disturbance factors, enhance ecosystem and social system spread and persistence.
Cycles built from the by-products of traits, naturally selected at lower levels, avoid conflict between levels and types of selection.
Since Darwin, individuals and more recently genes, have been the focus of evolutionary thinking. The idea that selection operates on non-reproducing,
higher-level systems including ecosystems or societies, has met with scepticism. But research emphasising that natural selection can be based solely on
differential persistence invites reconsideration of their evolution. Self-perpetuating feedback cycles involving biotic as well as abiotic components are critical
to determining persistence. Evolution of autocatalytic networks of molecules is well studied, but the principles hold for any ‘self-perpetuating’ system. Ecosystem
examples include coral reefs, rainforests, and savannahs. Societal examples include agricultural systems, dominant belief systems, and economies. Persistence-based
selection of feedbacks can help us understand how ecological and societal systems survive or fail in a changing world.
Objectives: Ethnic disparities in hypertension prevalence are well documented, though the influence of genetic ancestry is unclear. The aim of
this study was to evaluate associations of geographic genetic ancestry with hypertension and underlying blood pressure traits.
Methods: We tested genetically inferred ancestry proportions from five 1000 Genomes reference populations (GBR, PEL, YRI, CHB, and
LWK)for association with four continuous blood pressure (BP) traits (SBP,DBP, PP, MAP) and the dichotomous outcomes
hypertension and apparent treatment-resistant hypertension in 220 495 European American, 59 927 African American, and 21 273 Hispanic American individuals
from the Million Veteran Program. Ethnicity stratified results were meta-analyzed to report effect estimates per 10% difference for a given ancestry proportion in
all samples.
Results: Percentage GBR was negatively associated with BP (p = 2.13 × 10–19,
7.92 × 10–8, 4.41 × 10–11, and 3.57 × 10–13 for SBP,DBP, PP, and MAP, respectively; coefficient range -0.10 to -0.21 mmHg per 10% increase in ancestry proportion) and was protective against
hypertension [P = 2.59 × 10–5, odds ratio (OR) = 0.98] relative to other ancestries. YRI percentage was positively
associated with BP (p= 1.63 × 10–23, 1.94 × 10–26, 0.012, and 3.26 × 10–29 for SBP,DBP, PP, and MAP, respectively; coefficient range 0.06–0.32 mmHg per 10%
increase in ancestry proportion) and was positively associated with hypertension risk (p = 3.10 × 10–11, OR = 1.04) and apparent treatment-resistant
hypertension risk (p = 1.86 × 10–4, OR = 1.04) compared with other ancestries. Percentage PEL was
inverselyassociated with DBP (p = 2.84 × 10–5, beta = −0.11 mmHg per 10% increase in ancestry
proportion).
Conclusion: These results demonstrate that risk for BP traits varies significantly by genetic ancestry. Our findings provide insight into the
geographic origin of genetic factors underlying hypertension risk and establish that a portion of BP trait ethnic disparities are because of genetic differences
between ancestries.
This chapter contextualizes the dog-human relationship in the dog’s origin as a scavenger on the fringes of human settlements over 15,000 years ago. It then
reviews the evidence for unique evolved cognitive structures in dogs that could explain their success in a human-dominated world.
Failing to find evidence of unique human-like social-cognitive capacities I then review uncontroversial facts of dogs’ basic behavioral biology, including
reproductive and foraging behavior and, particularly, affiliative and attachment-related behaviors. This leads to consideration of dogs’ social behavior, both
conspecific and toward other species, especially humans.
I draw attention to a seldom-noted apparent contradiction between dogs’ stronger affectional bonds toward humans than toward members of their own species. Dogs’
social groups also show steeper social hierarchies accompanied by more behaviors indicating formal dominance than do other canid species including wolves.
I resolve this contradiction by proposing that dogs’ intense sensitivity to social hierarchy contributes to their willingness to accept human leadership. People
commonly control resources that dogs need and also unknowingly express behaviors which dogs perceive as formal signs of dominance. This may be what Darwin was
referring to when he endorsed the idea that a dog looks on his master as on a god.
Whatever the merits of this idea, if it serves to redirect behavioral research on dogs in human society more toward the social interactions of these species in
their diverse forms of symbiosis it will have served a useful function.
Genetic quality may be expressed through many traits simultaneously, and this would suggest a phenotype-wide fitness factor. In humans, intelligence has been
positively associated with several potential indicators of genetic quality, including ejaculate quality. We conducted a conceptual replication of one such study by
investigating the relationship between intelligence (assessed by the Raven Advanced Progressive Matrices Test-Short Form) and ejaculate quality (indexed by sperm
count, sperm concentration, and sperm motility) in a sample of 41 men (ages ranging 18 to 33 years; M = 23.33; SD = 3.60). By self-report, participants had not had
a vasectomy, and had never sought infertility treatment. We controlled for several covariates known to affect ejaculate quality (eg. abstinence duration before
providing an ejaculate) and found no statistically-significant relationship between intelligence and ejaculate quality; our findings, therefore, do not match those
of Arden, Gottfredson, Miller et al or those of previous studies. We discuss limitations of this study and the general research area and highlight the need for
future research in this area, especially the need for larger data sets to address questions around phenotypic quality and ejaculate quality.
…An important limitation of the current research is the small sample of 41 men, as small sample sizes increase the risk of both Type I and Type II errors. Our
analyses, therefore, may have lacked sufficient power to detect the small effect sizes, r = 0.14 to 0.19, reported by Arden, Gottfredson, Miller, and Pierce (2009). Small sample sizes
are a recurrent limitation of psychological research investigating ejaculate quality (eg. Baker & Bellis, 1989; Pook et al 2005), perhaps due to
difficulties recruiting participants outside a clinical setting. Arden, Gottfredson, Miller, and Pierce analyzed data from a sample of 425 men, which afforded the
analyses over 80% power to detect small effects. However, it is important to note that the correlation coefficients we obtained were similar in magnitude to those
reported by Arden, Gottfredson, Miller, and Pierce, ranging from −0.18 to 0.30, and the repeated-measures nature of our study gave it greater power despite the
small sample size.
2020-margaryan.pdf: “Population genomics of the Viking world”,
Ashot Margaryan, Daniel J. Lawson, Martin Sikora, Fernando Racimo, Simon Rasmussen, Ida Moltke, Lara M. Cassidy, et al (2020-09-16):
The maritime expansion of Scandinavian populations during the Viking Age (about AD 750–1050) was a far-flung transformation in world history1,2. Here
we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of
this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with
diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx
into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia
during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family
members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past
millennium, and trace positively selected loci—including the lactase-persistence allele of LCT and alleles of
ANKA that are associated with the immune response—in detail. We conclude that the Viking diaspora was characterized by
substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased
contact with the rest of the continent.
Technological advances in genetic testing have enabled prospective parents to learn about their risk of passing a genetic condition to their future children.
One option for those who want to ensure that their biological children do not inherit a genetic condition is to create embryos through in vitro fertilisation
(IVF) and use atechnique called preimplantation genetic testing (PGT) to
screen embryos for genetic abnormalities before implantation. Unfortunately, due to its high cost, IVF-with-PGT is out of reach for the vast majority of Americans. This article addresses an issue
that has been underexplored in the medical ethics literature: the lack of insurance coverage for IVF-with-PGT.Within the US system, a key concept in insurance is that of medically necessary care, which broadly consists of diagnostic
services and treatment services. In this article, I argue that IVF-with-PGT could be
classified as either a diagnostic service or as a treatment service. To make this case, I show that IVF-with-PGT is similar to other types of services that are often covered by US insurance
providers. In light of these similarities, I argue that the current system is inconsistent with respect to what is—and is not—covered by insurance. To promote
consistency and fairness in coverage, like cases should be treated alike—starting with greater coverage for IVF-with-PGT.
Natural selection is a key mechanism of evolution, which results from the differential reproduction of individuals due to differences in phenotype. We describe
fecundity selection on 13 anthropometric traits in a sample of 4000–10,000 of Estonian girls, who were born between 1937 and 1962 and measured at around 13 years
of age. Direct selection favoured shorter, slimmer and lighter girls with smaller heads, more masculine facial and body shapes and slower rates of sexual
maturation. Selection was stabilizing for weight, body mass index and face roundness. Direct selection was absent on two markers of general health and
viability—handgrip strength and vital lung capacity—although these traits experience negative indirect selection due to their association with educational
attainment. Similarly, indirect selection, mediated by educational attainment, accounted for a substantial portion of selection for girls with smaller heads,
narrower faces, and higher shoulder/hip ratios. These traits are thus subject to gene-culture coevolution, in that selection on body dimensions arises via
cultural and behavioural mechanisms.
In the twentieth century a conflict arose between geneticists and practical breeders over which theory of heredity should direct animal breeding strategies and
methods. Two different approaches existed and competed with each other over how to develop a breeding methodology for the livestock industries. This article
addresses strategies on the basis of theoretical outlooks by explaining the way they arose over the eighteenth and nineteenth centuries, what brought them into
conflict with each other after the rise of Mendelian genetics in 1900, and ultimately how and why the differing systems emanating from them affected animal
industries over the twentieth and into the twenty-first century. Looking at methodology through the lens of its theoretical roots provides an enriched appreciation
of the interrelationship between science and practice, and also shows that the intellectual disagreements between geneticists and practical breeders rested on
foundations that far predated the science of genetics.
Adult height is one of the earliest putative examples of polygenic adaptation in humans. However, this conclusion was recently challenged because residual
uncorrected stratification from large-scale consortium studies was considered responsible for the previously noted genetic difference. It thus remains an open
question whether height loci exhibit signals of polygenic adaptation in any human population. We re-examined this question, focusing on one of the shortest
European populations, the Sardinians, in addition to mainland European populations. We utilized height-associated loci from the Biobank Japan (BBJ) dataset to further alleviate concerns of biased ascertainment ofGWAS loci and showed that the Sardinians remain statistically-significantly shorter than expected under neutrality
(~0.22 standard deviation shorter than Utah residents with ancestry from northern and western Europe [CEU] on the basis
of polygenic height scores, p = 3.89 × 10−4). We also found the trajectory of polygenic height scores between the Sardinian and the
British populations diverged over at least the last 10,000 years (p = 0.0082), consistent with a signature of polygenic adaptation driven primarily by the
Sardinian population. Although the polygenic score-based analysis showed a much subtler signature in mainland European populations, we found a clear and robust
adaptive signature in the UK population by using a haplotype-based statistic, the
trait singleton density score (tSDS), driven by the height-increasing alleles (p = 9.1 × 10−4). In
summary, by ascertaining height loci in a distant East Asian population, we further supported the evidence of polygenic adaptation at height-associated loci among
the Sardinians. In mainland Europeans, the adaptive signature was detected in haplotype-based analysis but not in polygenic score-based analysis.
[Keywords: height, polygenic adaptation, population stratification]
Key message: Genomic selection using data from an on-going breeding program can improve gain from selection, relative to phenotypic selection,
by substantially increasing the number of lines that can be evaluated.
The early stages of phenotyping involve few observations and can be quite inaccurate. Genomic selection (GS) could improve selection accuracy and alter resource
allocation. Our objectives were (1) to compare the prediction accuracy of GS and phenotyping in stage-1 and stage-2 field evaluations and (2) to assess the value
of stage-1 phenotyping for advancing lines to stage-2 testing. We built training populations from 1769 wheat breeding lines that were genotyped and phenotyped for
yield, test weight, Fusarium head blight resistance, heading date, and height. The lines were in cohorts, and analyses were done by cohort. Phenotypes or GS
estimated breeding values were used to determine the trait value of stage-1 lines, and these values were correlated with their phenotypes from stage-2 trials. This
was repeated for stage-2 to stage-3 trials. The prediction accuracy of GS and phenotypes was similar to each other regardless of the amount (0, 50, 100%) of
stage-1 data incorporated in the GS model. Ranking of stage-1 lines by GS predictions that used no stage-1 phenotypic data had marginally lower correspondence to
stage-2 phenotypic rankings than rankings of stage-1 lines based on phenotypes. Stage-1 lines ranked high by GS had slightly inferior phenotypes in stage-2 trials
than lines ranked high by phenotypes. Cost analysis indicated that replacing stage-1 phenotyping with GS would allow nearly three times more stage-1 candidates to
be assessed and provide 0.84–2.23× greater gain from selection. We conclude that GS can complement or replace phenotyping in early stages of phenotyping.
Dizygotic twinning, the simultaneous birth of siblings when multiple ova are released, is an evolutionary paradox. Twin-bearing mothers often have elevated
fitness, but despite twinning being heritable, twin births occur only at low frequencies in human populations. We resolve this paradox by showing that twinning and
non-twinning are not competing strategies; instead, dizygotic twinning is the outcome of an adaptive conditional ovulatory strategy of switching from single to
double ovulation with increasing age. This conditional strategy, when coupled with the well-known decline in fertility as women age, maximizes reproductive success
and explains the increase and subsequent decrease in the twinning rate with maternal age that is observed across human populations. We show that the most
successful ovulatory strategy would be to always double ovulate as an insurance against early fetal loss, but to never bear twins. This finding supports the
hypothesis that twinning is a by-product of selection for double ovulation rather than selection for twinning.
In the following article, we forward the coalitional value theory (CVT) and apply it to several puzzles about human
behavior. The CVT contends that humans evolved unique mental mechanisms for assessing each other’s marginal value to a
coalition (ie., each other’s coalitional value). They defer to those with higher coalitional value, and they assert themselves over those with lower. We discuss
how this mechanism likely evolved. We note that it helps explains how human groups can expand into large, complicated, and specialized coalitions (chiefdoms and
even nation states). And we combine this with strong evidence that suggests that status striving is a fundamental human motive to explain partially (1) anti-gay
bias, (2) cultural signaling, (3) cultural conceptions of god, and (4) ideological conflict.
Since the development of single-hybrid maize breeding programs in the first half of the twentieth century1, maize yields have increased over
seven-fold, and much of that increase can be attributed to tolerance of increased planting density2,3,4. To explore the genomic basis underlying the
dramatic yield increase in maize, we conducted a comprehensive analysis of the genomic and phenotypic changes associated with modern maize breeding through
chronological sampling of 350 elite inbred lines representing multiple eras of germ-plasm from both China and the United States. We document several convergent
phenotypic changes in both countries. Using genome-wide association and selection scan methods, we identify 160 loci underlying adaptive agronomic phenotypes and
more than 1,800 genomic regions representing the targets of selection during modern breeding. This work demonstrates the use of the breeding-era approach for
identifying breeding signatures and lays the foundation for future genomics-enabled maize breeding.
This research applied genomics and phenotypic information in three different beef cattle populations. The methods applied were association analyses, runs of
homozygosity, and genetic correlations. This incorporated both genomic and phenotypic approaches to identify the results of linebreeding in two closed Hereford
populations. Further work evaluated carcass and maternal traits from the American Simmental Association Carcass Merit Program using genomic and phenotypic
information to identify how carcass-based selection decisions impact maternal performance of Simmental-based cattle. Line 4 pedigree inbreeding, genomic
inbreeding, and genomic pedigree inbreeding ranges were 0–36%, 0–49%, and 0–29%, respectively, and average inbreeding was 12.6%, 12.3%, and 17.7%, respectively.
Line 1 pedigree inbreeding, genomic inbreeding, and genomic pedigree inbreeding ranges were 0–71%, 0–46%, and 0–63%, respectively, and average inbreeding was
42.1%, 14.4%, and 31.0%, respectively. Average rate of change in inbreeding per year was 0.03% over 55 years for Line 4 and −0.03% over 83 years for Line 1.
Identified for Line 4 were 45 ROH regions, 35 strongly statistically-significant single nucleotidepolymorphisms, three strongly statistically-significant SNP withinROH,
and some statistically-significant SNP within 12 previouslyidentified genes. Identified for Line 1 were 50
ROH regions, 93strongly statistically-significant SNP, three stronglystatistically-significant SNP within ROH, and somestatistically-significant SNP within 11 previously identified genes. Within the Simmental dataset, nine
chromosomes had genome-wide statistical-significance, explaining 0.2142% of total phenotypic information. The single-locus model identified 365 novel regions and
251 novel positional candidate genes. The multi-locus model identified 393 novel regions and 283 novel positional candidate genes. Also, detrimental genetic
correlations between carcass characteristics and maternal traits were less than previously reported. Analyses utilized in this study indicate ROH and statistically-significant SNP can be used to identify regions of the genome affected by
inbreeding. Also, simultaneous selection for carcass and maternal traits reduced the negative impact seen with single-trait selection for carcass traits.
The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models
for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinicalisolate of
SARS-CoV-2 by serial passaging in the respiratory tract ofaged BALB/c mice.
The resulting mouse-adapted strain at passage 6(called MASCp6) showed increased infectivity in mouse lung and led
to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive
mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protectiveefficacy of a recombinant RBD vaccine candidate
was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals
against SARS-CoV-2.
In the past, most biologists, myself included, did not think of evolution as changing over time. The wonders of natural selection were always at hand and went
into operation once there was life. However, with a little reflection it becomes obvious that evolution has changed—there has been an evolution of evolution.
Evolution can be separated into four phases, or eras, that may or may not overlap. The first era starts with the evolution of life on earth, which led to
single cells that multiply asexually. The second era takes advantage of the invention of sexual reproduction as evolution could now gallop forward because
of a richer fare of diverse offspring for natural selection. The third era begins with the introduction of multicellularity. In the fourth era
there is a radical innovation: the nervous system that arises animals by standard Darwinian selection. This has allowed major rapid changes to proceed, such as
language that led to all the rapid progress we call civilization; a true revolution, and one that does not depend on the slow genetic changes of all other standard
gene-controlled evolutionary steps.
Global exposures to air pollution and cigarette smoke are novel in human evolutionary history and are associated with at least 12 million premature deaths per
year. We investigate the history of the human exposome for relationships between novel environmental toxins and genetic changes during human evolution in
6 phases:
Phase I: With increased walking on savannas, early human ancestors inhaled crustal dust, fecal aerosols, and spores; carrion scavenging introduced new
infectious pathogens.
Phase II: Domestic fire exposed early Homo to novel toxins from smoke and cooking.
Phases III and IV: Neolithic to preindustrialHomo sapiens incurred infectious pathogens from
domestic animals and dense communities with limited sanitation.
Phase V: Industrialization introduced novel toxins from fossil fuels, industrial chemicals, and tobacco at the same time infectious pathogens were
diminishing. Thereby, pathogen-driven causes of mortality were replaced by chronic diseases driven by sterile inflammogens, exogenous and endogenous.
Phase VI: Considers future health during global warming with increased air pollution and infections.
We hypothesize that adaptation to some ancient toxins persists in genetic variations associated with inflammation and longevity.
[Keywords: exposome, human evolution, genes, toxins, infections]
IVF embryos could be profiled with polygenic scores for traits such as height or IQ
The top-scoring embryo is expected to be ≈2.5 cm or ≈2.5 IQ points above the average
The adult trait value of the top-scoring embryo would remain widely distributed
Multiple ethical and other factors impose practical limits on the actual gain
The increasing proportion of variance in human complex traits explained by polygenic scores, along with progress in preimplantation genetic diagnosis, suggests
the possibility of screening embryos for traits such as height or cognitive ability. However, the expected outcomes of embryo screening are unclear, which
undermines discussion of associated ethical concerns. Here, we use theory, simulations, and real data to evaluate the potential gain of embryo screening, defined
as the difference in trait value between the top-scoring embryo and the average embryo. The gain increases very slowly with the number of embryos but more rapidly
with the variance explained by the score. Given current technology, the average gain due to screening would be ≈2.5 cm for height and ≈2.5 IQ points for cognitive
ability. These mean values are accompanied by wide prediction intervals, and indeed, in large nuclear families, the majority of children top-scoring for height are
not the tallest.
Copy number variants (CNVs) are subject to stronger selective pressure than single-nucleotide variants, but their roles in archaic introgression and
adaptation have not been systematically investigated. We show that stratified CNVs are
statistically-significantly associated with signatures of positive selection in Melanesians and provide evidence for adaptive introgression of large CNVs at chromosomes 16p11.2 and 8p21.3 from Denisovans and Neanderthals, respectively. Using long-read sequence data, we
reconstruct the structure and complex evolutionary history of these polymorphisms and show that both encode positively selected genes absent from most human
populations. Our results collectively suggest that large CNVs originating in archaic hominins and
introgressed into modern humans have played an important role in local population adaptation and represent an insufficiently studied source of large-scale genetic
variation.
The ability of parasites to manipulate host behavior to their advantage has been studied extensively, but the impact of parasite manipulation on the evolution
of neural and endocrine mechanisms has remained virtually unexplored. If selection for countermeasures has shaped the evolution of nervous systems, many aspects of
neural functioning are likely to remain poorly understood until parasites—the brain’s invisible designers—are included in the picture.
This article offers the first systematic discussion of brain evolution in light of parasite manipulation. After reviewing the strategies and mechanisms employed
by parasites, the paper presents a taxonomy of host countermeasures with four main categories, namely: restrict access to the brain; increase the costs of
manipulation; increase the complexity of signals; and increase robustness. For each category, possible examples of countermeasures are explored, and the likely
evolutionary responses by parasites are considered.
The article then discusses the metabolic, computational, and ecological constraints that limit the evolution of countermeasures. The final sections offer
suggestions for future research and consider some implications for basic neuroscience and psychopharmacology.
The paper aims to present a novel perspective on brain evolution, chart a provisional way forward, and stimulate research across the relevant disciplines.
A strong selective sweep at TRPS1 occurred in African rainforest hunter-gatherers
Pleiotropic height genes lead to polygenic selection signals for reproductive age
Pathogen-driven selection, mostly viral, has been pervasive among hunter-gatherers
Post-admixture selection has maintained adaptive variation in hunter-gatherers
Summary: African rainforests support exceptionally high biodiversity and host the world’s largest number of active hunter-gatherers [1, 2, 3]. The
genetic history of African rainforest hunter-gatherers and neighboring farmers is characterized by an ancient divergence more than 100,000 years ago, together with
recent population collapses and expansions, respectively [4, 5, 6, 7, 8, 9, 10, 11, 12]. While the demographic past of rainforest hunter-gatherers has been deeply
characterized, important aspects of their history of genetic adaptation remain unclear. Here, we investigated how these groups have adapted—through classic
selective sweeps, polygenic adaptation, and selection since admixture—to the challenging rainforest environments. To do so, we analyzed a combined dataset of 566
high-coverage exomes, including 266 newly generated exomes, from 14 populations
of rainforest hunter-gatherers and farmers, together with 40 newly generated, low-coverage genomes. We find evidence for a strong, shared selective sweep among all
hunter-gatherer groups in the regulatory region of TRPS1—primarily involved in morphological traits. We detect strong
signals of polygenic adaptation for height and life history traits such as reproductive age; however, the latter appear to result from pervasive pleiotropy of
height-associated genes. Furthermore, polygenic adaptation signals for functions related to responses of mast cells to allergens and microbes, the IL-2 signaling
pathway, and host interactions with viruses support a history of pathogen-driven selection in the rainforest. Finally, we find that genes involved in heart and
bone development and immune responses are enriched in both selection signals and local hunter-gatherer ancestry in admixed populations, suggesting that selection
has maintained adaptive variation in the face of recent gene flow from farmers.
In those early days, the company, just like almost everybody else in Washington, primarily produced Red Delicious apples, plus a few Goldens and
Grannies—familiar workhorse varieties that anybody was allowed to grow. Back then, the state apple commission advertised its wares with a poster of a stoplight:
one apple each in red, green, and yellow. Today, across more than 4,000 acres of McDougall apple trees, you won’t find a single Red; every year, you’ll also find
fewer acres of the apples that McDougall calls “core varieties”, the more modern open-access standards such as Gala and Fuji. Instead, McDougall is betting on what
he calls “value-added apples”: Ambrosias, whose rights he licensed from a Canadian company; Envy, Jazz, and Pacific Rose, whose intellectual properties are owned
by the New Zealand giant Enzafruit; and a brand-new variety, commercially available for the first time this year and available only to Washington-state growers:
the Cosmic Crisp.
…The Cosmic Crisp is debuting on grocery stores after this fall’s harvest, and in the nervous lead-up to the launch, everyone from nursery operators to
marketers wanted me to understand the crazy scope of the thing: the scale of the plantings, the speed with which mountains of commercially untested fruit would be
arriving on the market, the size of the capital risk. People kept saying things like “unprecedented”, “on steroids”, “off the friggin’ charts”, and “the largest
launch of a single produce item in American history.”
McDougall took me to the highest part of his orchard, where we could look down at all its hundreds of very expensively trellised and irrigated acres (he
estimated the costs to plant each individual acre at $60,000 to $65,000, plus another $12,000 in operating costs each year), their neat, thin lines of trees like
the stitching over so many quilt squares. “If you’re a farmer, you’re a riverboat gambler anyway”, McDougall said. “But Cosmic Crisp—woo!” I thought of the warning
of one former fruit-industry journalist that, with so much on the line, the enormous launch would have to go flawlessly: “It’s gotta be like the new iPhone.”
…Though Washington State University owns the WA 38 patent, the breeding program has received funding from the apple industry, so it was agreed, over some
objections by people who worried that quality would be diluted, that the variety should be universally and exclusively available to Washington growers. (Growers of
Cosmic Crisp pay royalties both on every tree they buy and on every box they sell, money that will fund future breeding projects as well as the shared
marketing campaign.) The apple tested so well that WSU, in collaboration with commercial nurseries, began
producing apple saplings as fast as possible; the plan was to start with 300,000 trees, but growers requested 4 million, leading to a lottery for divvying up the
first available trees. Within three years, the industry had sunk 13 million of them, plus more than half a billion dollars, into the ground. Proprietary Variety
Management expects that the number of Cosmic Crisp apples on the market will grow by millions of boxes every year, outpacing Pink Lady and Honeycrisp within about
five years of its launch.
Many traits of interest are highly heritable and genetically complex, meaning that much of the variation they exhibit arises from differences at numerous loci
in the genome. Complex traits and their evolution have been studied for more than a century, but only in the last decade have genome-wide association studies
(GWASs) in humans begun to reveal their genetic basis. Here, we bring these threads of research together to ask
how findings from GWASs can further our understanding of the processes that give rise to heritable variation in complex
traits and of the genetic basis of complex trait evolution in response to changing selection pressures (ie., of polygenic adaptation). Conversely, we ask how
evolutionary thinking helps us to interpret findings from GWASs and informs related efforts of practical
importance.
Some 80% of active sniffer dogs deployed by South Korea’s quarantine agency are cloned, data showed Monday, as activists express their concerns over potential
animal abuse. According to the Animal and Plant Quarantine Agency, 42 of its 51 sniffer dogs were cloned from parent animals as of April, indicating such cloned
detection dogs are already making substantial contributions to the country’s quarantine activities. The number of cloned dogs first outpaced their naturally born
counterparts in 2014, the agency said. Of the active cloned dogs, 39 are currently deployed at Incheon International Airport, the country’s main gateway.
Deploying cloned dogs can save time and money over training naturally born puppies as they maintain the outstanding traits of their parents, whose capabilities
have already been verified in the field, according to experts. While the average cost of raising one detection dog is over 100 million won (US$85,600), it is less
than half that when utilising cloned puppies, they said.
Inbreeding depression is a growing concern in livestock because it can
detrimentally affect animal fitness, health, and production levels.
Genomic information can be used to more effectively capture variance in Mendelian sampling, thereby enabling more
accurate estimation of inbreeding, but further progress is still required. The
calculation of inbreeding for herd management purposes is largely still done using pedigree information only, although inbreeding
coefficients calculated in this manner have been shown to be less accurate than genomic inbreeding measures. Continuous stretches of homozygous genotypes, so called “runs of homozygosity”, have been shown to provide a better estimate of autozygosity at the genomic level than conventional measures based
on inbreeding coefficients calculated through conventional pedigree information or even genomic relationship matrices. For improved and targeted management of
genomic inbreeding at the population level, the development of methods that incorporate genomic information in mate selection programs may provide a more precise
tool for reducing the detrimental effects of inbreeding in dairy herds. Additionally, a better understanding of the genomic architecture of inbreeding and
incorporating that knowledge into breeding programs could substantially refine current practices.
Opportunities to maintain high levels of genetic progress in traits of interest while managing homozygosity and sustaining acceptable levels of heterozygosity in highly selected dairy
populations exist and should be examined more closely for continued sustainability of both the dairy cattle population as well as the dairy industry. The inclusion
of precise genomic measures of inbreeding, such as runs of homozygosity, inbreeding, and mating programs, may provide a path forward.
In this symposium review article, we describe traditional measures of inbreeding and the recent developments made toward more precise measures of homozygosity
using genomic information. The effects of homozygosity resulting from inbreeding on phenotypes, the identification and mapping of detrimental homozygosity haplotypes, management of inbreeding with genomic data, and areas in need of further research
are discussed.
[Keywords: inbreeding, runs of homozygosity, mating programs]
40 years ago, Gould and Lewontin used the metaphor of a building’s “spandrels” to highlight that organismal traits could be the inevitable consequence of organismal construction, with no alternative
configurations possible. Because adaptation by natural selection requires variation, regarding a trait incapable of variation as an adaptation could be a serious
error. Gould and Lewontin’s exhortation spurred biologists’ efforts to investigate biases and limitations in development in their studies of adaptation, a major
methodological advance.
But in terms of the metaphor itself, over the past 40 years there are virtually no examples of “spandrels” in the primary literature. Moreover, multiple serious confusions in the metaphor have been identified and clarified, for example,
that the “spandrels” of San Marco are pendentives, and pendentives are perfect examples
of adaptation.
I look back over the sparse empirical fruits of the “spandrels” metaphor, and ask what the clarifications of the past 40 years mean for biological theory and
practice. I conclude that if there is anything to be rescued from the clarified spandrels metaphor, it is not “constraint” at all.
Instead, it is the still-unresolved issue of trait delimitation, which is how to parse organisms into subsets that are tractable and biologically appropriate
for study.
Large-scale phylogenetic studies of animal cognition have revealed robust links between absolute brain volume and species differences in executive function.
However, past comparative samples have been composed largely of primates, which are characterized by evolutionarily derived neural scaling rules. Therefore, it is
currently unknown whether positive associations between brain volume and executive function reflect a broad-scale evolutionary phenomenon, or alternatively, a unique consequence of primate
brain evolution. Domestic dogs provide a powerful opportunity for investigating this question due to their close genetic relatedness, but vast intraspecific
variation. Using citizen science data on more than 7000 purebred dogs from 74 breeds, and controlling for genetic relatedness between breeds, we identify strong
relationships between estimated absolute brain weight and breed differences in cognition. Specifically, larger-brained breeds performed statistically-significantly
better on measures of short-term memory and self-control. However, the relationships between estimated brain weight and other cognitive measures varied widely,
supporting domain-specific accounts of cognitive evolution. Our results suggest that evolutionary increases in brain size are positively associated with taxonomic
differences in executive function, even in the absence of primate-like neuroanatomy. These findings also suggest that
variation between dog breeds may present a powerful model for investigating correlated changes in neuroanatomy and cognition among closely related taxa.
The Canadian Inuit have a distinct population background that may entail particular implications for the health of its individuals. However, the number of
genetic studies examining this Inuit population is limited, and much remains to be discovered in regard to its genetic characteristics. In this study, we generated
whole-exome sequences and genomewide genotypes for 170 Nunavik Inuit, a small and isolated founder population of Canadian Arctic indigenous people. Our study
revealed the genetic background of Nunavik Inuit to be distinct from any known present-day population. The majority of Nunavik Inuit show little evidence of gene
flow from European or present-day Native American peoples, and Inuit living around Hudson Bay are genetically distinct from those around Ungava Bay. We also
inferred that Nunavik Inuit have a small effective population size of 3,000 and likely split from Greenlandic Inuit ~10.5 kya. Nunavik Inuit went through a
bottleneck at approximately the same time and might have admixed with a population related to the Paleo-Eskimos. Our study highlights population-specific genomic
signatures in coding regions that show adaptations unique to Nunavik Inuit, particularly in pathways involving fatty acid metabolism and cellular adhesion
(CPNE7, ICAM5, STAT2, and
RAF1). Subsequent analyses in selection footprints and the risk of intracranial aneurysms (IAs) in Nunavik Inuit
revealed an exonic variant under weak negative selection to be statistically-significantly associated with IA (rs77470587; P = 4.6 × 10−8).
Cryptic genetic variation can facilitate adaptation in evolving populations. To elucidate the underlying genetic mechanisms, we used directed evolution in
Escherichia coli to accumulate variation in populations of yellow fluorescent proteins and then evolved these proteins toward the new phenotype of green
fluorescence. Populations with cryptic variation evolved adaptive genotypes with greater diversity and higher fitness than populations without cryptic variation,
which converged on similar genotypes. Populations with cryptic variation accumulated neutral or deleterious mutations that break the constraints on the order in
which adaptive mutations arise. In doing so, cryptic variation opens paths to adaptive genotypes, creates historical contingency, and reduces the predictability of
evolution by allowing different replicate populations to climb different adaptive peaks and explore otherwise-inaccessible regions of an adaptive landscape.
Humans cause widespread evolutionary change in nature, but we still know little about the genomic basis of rapid adaptation in the Anthropocene. We tracked
genomic changes across all protein-coding genes in experimental fish populations that evolved pronounced shifts in growth rates due to size-selective harvest over
only four generations. Comparisons of replicate lines show parallel allele frequency shifts that recapitulate responses to size-selection gradients in the wild
across hundreds of unlinked variants concentrated in growth-related genes. However, a supercluster of genes also rose rapidly in frequency and dominated the
evolutionary dynamic in one replicate line but not in others. Parallel phenotypic changes thus masked highly divergent genomic responses to selection, illustrating
how contingent rapid adaptation can be in the face of strong human-induced selection.
While many studies have highlighted human adaptations to diverse environments worldwide, genomic studies of natural selection in Indigenous populations in the
Americas have been absent from this literature until very recently. Since humans first entered the Americas some 20,000 years ago, they have settled in many new
environments across the continent. This diversity of environments has placed variable selective pressures on the populations living in each region, but the effects
of these pressures have not been extensively studied to date. To help fill this gap, we collected genome-wide data from three Indigenous North American populations
from different geographic regions of the continent (Alaska, southeastern United States, and central Mexico). We identified signals of natural selection in each
population and compared signals across populations to explore the differences in selective pressures among the three regions sampled. We find evidence of
adaptation to cold and high-latitude environments in Alaska, while in the southeastern United States and central Mexico, pathogenic environments seem to have
created important selective pressures. This study lays the foundation for additional functional and phenotypic work on possible adaptations to varied environments
during the history of population diversification in the Americas.
Evolutionary rates and strength of selection differ markedly between haploid and diploid genomes. Any genes expressed in a haploid state will be directly
exposed to selection, whereas alleles in a diploid state may be partially or fully masked by a homologous allele. This difference may shape key evolutionary
processes, including rates of adaptation and inbreeding depression, but also the evolution of sex chromosomes, heterochiasmy, and stable sex ratio biases. All
diploid organisms carry haploid genomes, most notably the haploid genomes in gametes produced by every sexually reproducing eukaryote. Furthermore, haploid
expression occurs in genes with monoallelic expression, in sex chromosomes, and in organelles, such as mitochondria and plastids. A comparison of evolutionary
rates among these haploid genomes reveals striking parallels. Evidence suggests that haploid selection has the potential to shape evolution in predominantly
diploid organisms, and taking advantage of the rapidly developing technologies, we are now in the position to quantify the importance of such selection on haploid
genomes.
2019-hickey.pdf: “Breeding crops to feed 10 billion”, Lee
T. Hickey, Amber Hafeez, Hannah Robinson, Scott A. Jackson, Soraya C. M. Leal-Bertioli, Mark Tester, et al (2019-01-01)
The ruminants are one of the most successful mammalian lineages, exhibiting morphological and habitat diversity and containing several key livestock species. To
better understand their evolution, we generated and analyzed de novo assembled genomes of 44 ruminant species, representing all six Ruminantia families. We used
these genomes to create a time-calibrated phylogeny to resolve topological controversies, overcoming the challenges of incomplete lineage sorting. Population
dynamic analyses show that population declines commenced between 100,000 and 50,000 years ago, which is concomitant with expansion in human populations. We also
reveal genes and regulatory elements that possibly contribute to the evolution of the digestive system, cranial appendages, immune system, metabolism, body size,
cursorial locomotion, and dentition of the ruminants.
2019-barrett.pdf: “Linking a mutation to survival in wild mice”,
Rowan D. H. Barrett, Stefan Laurent, Ricardo Mallarino, Susanne P. Pfeifer, Charles C. Y. Xu, Matthieu Foll, et al (2019-01-01):
Adaptive evolution in new or changing environments can be difficult to predict because the functional connections between genotype, phenotype, and fitness are
complex. Here, we make these explicit connections by combining field and laboratory experiments in wild mice. We first directly estimate natural selection on
pigmentation traits and an underlying pigment locus, Agouti, by using experimental enclosures of mice on different soil colors. Next, we show how a
mutation in Agouti associated with survival causes lighter coat color through changes in its protein binding properties. Together, our findings
demonstrate how a sequence variant alters phenotype and then reveal the ensuing ecological consequences that drive changes in population allele frequency, thereby
illuminating the process of evolution by natural selection.
The canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and
survives by “metastasizing” between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We
constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage’s worldwide expansion.
Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer’s evolution but subsequently
vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process.
CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential
genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of
long-term cancer evolution.
We hypothesize that, ancestrally, sex-specific immune modulation evolved to facilitate survival of the pregnant person in the presence of an invasive placenta
and an immunologically challenging pregnancy—an idea we term the ‘pregnancy compensation hypothesis’ (PCH). Further, we
propose that sex differences in immune function are mediated, at least in part, by the evolution of gene content and dosage on the sex chromosomes, and are
regulated by reproductive hormones. Finally, we propose that changes in reproductive ecology in industrialized environments exacerbate these evolved sex
differences, resulting in the increasing risk of autoimmune disease observed in females, and a counteracting reduction in diseases such as cancer that can be
combated by heightened immune surveillance. The PCH generates a series of expectations that can be tested empirically
and that may help to identify the mechanisms underlying sex differences in modern human diseases.
The forecasting of the future growth of world population is of critical importance to anticipate and address a wide range of global challenges. The United
Nations produces forecasts of fertility and world population every two years. As part of these forecasts, they model fertility levels in post-demographic transition countries as tending toward a
long-term mean, leading to forecasts of flat or declining population in these countries.
We substitute this assumption of constant long-term fertility with a dynamic model, theoretically founded in evolutionary biology, with heritable fertility.
Rather than stabilizing around a long-term level for post-demographic transition countries, fertility tends to increase as
children from larger families represent a larger share of the population and partly share their parents’ trait of having more offspring.
Our results suggest that world population will grow larger in the future than currently anticipated.
[Keywords: fertility, evolution, population biology, evolutionary demography]
Superorganisms such as social insect colonies are very successful relative to their non-social counterparts. Powerful emergent information processing
capabilities would seem to contribute to their abundance, as they explore and exploit their environment collectively. In this series of three papers, we develop a
Bayesian model of collective information processing, starting here with nest-finding, then examining foraging (part II) and
externalized memories (pheromone territory markers) in part III. House-huntingTemnothorax ants are adept
at discovering and choosing the best available nest site for their colony. Essentially, we propose that they estimate the probability each choice is best, and then
choose the highest probability. Viewed this way, we propose that their behavioural algorithm can be understood as a sophisticated statistical method that predates
recent mathematical advances by some tens of millions of years. Here, we develop a model of their nest finding that incorporates insights from approximate Bayesian computation as a model of
collective estimation of alternative choices; and Thompson sampling, as an effective regret-minimizing decision-making rule by viewing nest choice in terms of a
multi-armed bandit problem (Robbins, 1952). Our
Bayesian framework points to the potential for further bio-inspired statistical techniques. It also facilitates the generation of hypotheses regarding individual
and collective movement behaviours when collective decisions must be made.
A consequence of sexual reproduction in eukaryotes is the evolution of a biphasic life cycle with alternating diploid and haploid gametic phases. While our
focus in evolutionary biology is on selection during the diploid phase, we know relatively little about selection occurring during the haploid gametic stage. This
is particularly true in predominantly diploid animals, where gene expression and hence selection have long been thought to be absent in haploid cells like gametes
and particularly sperm.
During my PhD, I tested the idea of selection during the haploid gametic phase using zebrafish Danio rario as a study species. I combined a large-scale selection experiment over 3 generations with fitness assays and
next-generation sequencing to assess the importance of haploid selection. We measured offspring fitness in all 3 generations. In addition, we compared gene
expression in brain and testes of F1 and F3 adult male from each treatment by RNA sequencing.
We found that offspring sired by longer-lived sperm showed higher survival rate and higher early-life and late-life reproductive fitness compared to offspring
sired by shorter-lived sperm. We also found differentially expressed genes between the 2 treatments with functions in metabolic and developmental pathways.
These findings suggest that the observed fitness differences to be caused by small expression changes in many basic genes. We also tested for a genetic
underpinning of the selected sperm phenotypes and identified allelic differences across the entire genome. Finally, we investigated the additive genetic component
and parental effect of different sperm phenotypes. We found generally low additive genetic variation and high parental effects on sperm performance traits.
In conclusion, this thesis provides evidence that the phenotypic variation among intact fertile sperm within an ejaculate affects offspring fitness throughout
life and provides a clear link between sperm phenotype and offspring fitness and between sperm phenotype and sperm genotype.
…List of Papers: This thesis is based on the following papers, which are referred to in the text by their Roman numerals.
I. Alavioon et al 2017, “Sperm selection within a single ejaculate increases offspring
fitness” II. Alavioon et al, “Within-ejaculate selection for sperm longevity reduces male reproductive ageing”. Manuscript III. Alavioon et al, “The fitness consequences of selection in haploid sperm across generations”. Manuscript IV. Alavioon et al,
“Sperm performance traits exhibit low heritability and strong parental effects in external fertilizer”. Manuscript.
Additional Papers:
The following papers were published/in publishing process during the course of my doctoral studies but are not part of the thesis.
Berg et al 2014, “Evolution of differential maternal age effects on male and female offspring development and longevity”
Promerova et al 2017, “No evidence for MHC class II-based disassortative mating at the gamete
level in Atlantic salmon”
Silva et al, “Perceived sperm competition intensity in zebrafish males affects gene expression in early offspring”. Manuscript
…The mechanisms and outcomes of selection occurring during diploid and haploid phases differ substantially (Crow & Kimura 1965). Because diploids have 2
copies of each allele, they can mask recessive mutations, which are therefore less exposed to selection. In contrast, when an allele is expressed in a haploid
state, it is entirely exposed to selection since there is no masking effect of a sister allele. This can in fact facilitate the rate of spreading and fixation of
beneficial alleles while reducing the accumulation of deleterious mutations in a population by efficiently eliminating deleterious mutations (Haldane 1924;
Crow & Kimura 1965; Mable & Otto 1998). …Haploid selection is a situation in which a phenotype under selection is determined by a haploid allele (Joseph
& Kirkpatrick 2004).
…in animals, haploid selection is understudied due to an existing dogma that gene expression at the post-meiotic haploid phase is largely absent. Many
researchers dismissed the possibility of haploid selection in animals for several reasons. The first reason was the fact that most animals spend the majority of
their life cycle as diploids followed by a very short haploid stage. The other reason was that the DNA in sperm/gametes
is densely packed and almost entirely lacking a cytoplasm, therefore haploid gene expression and translation (Kettaneh & Hartl 1976) are impossible and
sperm in basically transcriptionally silent (Steger 1999; Joseph & Kirkpatrick 2004). Although later on, researchers found evidence of post-meiotic
DNA transcription in sperm, they believed that the newly made transcriptomic products and other molecules could be
shared between sperm cells through cytoplasmic bridges (Jeon 2004), therefore, all sperm cells benefit from the similarly defined sperm traits and none of the
sperm develops advantages over others. Later on researchers found more proofs of DNA transcription
(Erickson et al 1981) and even small amounts of protein translation in sperm cells (Gur & Breitbart 2006; Gur & Breitbart 2007; Gur
& Breitbart 2008), and evidence that showed not all of the transcriptomes and proteins can be passed through cytoplasmic bridges
(Erickson et al 1981). They also found that the alterations of the epigenome of sperm after meiosis (Teperek et al 2016) cause
individual sperm to vary and to affect the next generation offspring differently. All these post-meiotic changes may form a basis for differences between
individual sperm and create a potential for haploid selection to occur. In 2004 a review on a few studies showed several loci in animals’ genome experience
haploid selection and it emphasized that such selection might potentially affect several evolutionary processes. Antagonistic adaptation between haploid and
diploid phases, sex specific recombination rates and genome imprinting, loads of deleterious mutations and extent of inbreeding depression are a few, among the
many ways that haploid selection can affect evolutionary processes (Charlesworth & Charlesworth 1987; Charlesworth et al 1993; Joseph &
Kirkpatrick 2004; Wyman & Wyman 2013).
[WP] Because of the intrinsic randomness of the evolutionary process,
a mutant with a fitness advantage has some chance to be selected but no certainty. Any experiment that searches for advantageous mutants will lose many of them due
to random drift. It is therefore of great interest to find population structures that improve the odds of advantageous mutants. Such structures are called
amplifiers of natural selection: they increase the probability that advantageous mutants are selected. Arbitrarily strong amplifiers guarantee the selection of
advantageous mutants, even for very small fitness advantage. Despite intensive research over the past decade, arbitrarily strong amplifiers have remained rare.
Here we show how to construct a large variety of them. Our amplifiers are so simple that they could be useful in biotechnology, when optimizing biological
molecules, or as a diagnostic tool, when searching for faster dividing cells or viruses. They could also occur in natural population structures.
In the evolutionary process, mutation generates new variants, while selection chooses between mutants that have different reproductive rates. Any new mutant is
initially present at very low frequency and can easily be eliminated by random
drift. The probability that the lineage of a new mutant eventually takes over the entire population is called the fixation probability. It is a key quantity of evolutionary dynamics and
characterizes the rate of evolution.
…In this work we resolve several open questions regarding strong amplification under uniform and temperature initialization. First, we show that there exists a
vast variety of graphs with self-loops and weighted edges that are arbitrarily strong amplifiers for both uniform and temperature initialization. Moreover, many of
those strong amplifiers are structurally simple, therefore they might be realizable in natural or laboratory setting. Second, we show that both self-loops and
weighted edges are key features of strong amplification. Namely, we show that without either self-loops or weighted edges, no graph is a strong amplifier under
temperature initialization, and no simple graph is a strong amplifier under uniform initialization.
…In general, the fixation probability depends not only on the graph, but also on the initial placement of the invading mutants…For a wide class of population
structures17, which include symmetric ones28, the fixation probability is the same as for the well-mixed population.
… A population structure is an arbitrarily strong amplifier (for brevity hereafter also called “strong amplifier”) if it ensures a fixation probability
arbitrarily close to one for any advantageous mutant, r > 1. Strong amplifiers can only exist in the limit of large population size.
Numerical studies30 suggest that for spontaneously arising mutants and small population size, many unweighted graphs amplify for some values of
r. But for a large population size, randomly constructed, unweighted graphs do not amplify31. Moreover, proven amplifiers for all values of
r are rare. For spontaneously arising mutants (uniform initialization): (1) the Star has fixation probability of ~1 − 1⁄r2 in the
limit of large N, and is thus an amplifier17, 32, 33; (2) the Superstar (introduced in ref. 17, see also ref. 34) and the Incubator
(introduced in refs. 35, 36), which are graphs with unbounded degree, are strong amplifiers.
…In this work we resolve several open questions regarding strong amplification under uniform and temperature initialization. First, we show that there exists a
vast variety of graphs with self-loops and weighted edges that are arbitrarily strong amplifiers for both uniform and temperature initialization. Moreover, many of
those strong amplifiers are structurally simple, therefore they might be realizable in natural or laboratory setting. Second, we show that both self-loops and
weighted edges are key features of strong amplification. Namely, we show that without either self-loops or weighted edges, no graph is a strong amplifier under
temperature initialization, and no simple graph is a strong amplifier under uniform initialization.
Figure 1: Evolutionary dynamics in structured populations. Residents (yellow) and mutants (purple) differ in their reproductive
rate. (a) A single mutant appears. The lineage of the mutant becomes extinct or reaches fixation. The probability that the mutant takes over
the population is called “fixation probability”. (b) The classical, well-mixed population is described by a complete graph with self-loops.
(Self-loops are not shown here.) (c) Isothermal structures do not change the fixation probability compared to the well-mixed population.
(d) The Star is an amplifier for uniform initialization. (e) A self-loop means the offspring can replace the parent.
Self-loops are a mathematical tool to assign different reproduction rates to different places. (f) The Superstar, which has unbounded degree
in the limit of large population size, is a strong amplifier for uniform initialization. Its edges (shown as arrows) are directed which means that the
connections are one-way.
Figure 4: Infinite variety of strong amplifiers. Many topologies can be turned into arbitrarily strong amplifiers (Wheel
(a), Triangular grid (b), Concentric circles (c), and Tree (d)). Each graph is partitioned
into hub (orange) and branches (blue). The weights can be then assigned to the edges so that we obtain arbitrarily strong amplifiers. Thick edges receive large
weights, whereas thin edges receive small (or zero) weights
…Intuitively, the weight assignment creates a sense of global flow in the branches, directed toward the hub. This guarantees that the first 2 steps happen with
high probability. For the third step, we show that once the mutants fixate in the hub, they are extremely likely to resist all resident invasion attempts and
instead they will invade and take over the branches one by one thereby fixating on the whole graph. For more detailed description, see “Methods” section
“Construction of strong amplifiers”.
Necessary conditions for amplification: Our main result shows that a large variety of population structures can provide strong amplification. A
natural follow-up question concerns the features of population structures under which amplification can emerge. We complement our main result by proving that both
weights and self-loops are essential for strong amplification. Thus, we establish a strong dichotomy. Without either weights or self-loops, no graph can be a
strong amplifier under temperature initialization, and no simple graph can be a strong amplifier under uniform initialization. On the other hand, if we allow both
weights and self-loops, strong amplification is ubiquitous.
…Some naturally occurring population structures could be amplifiers of natural selection. For example, the germinal centers of the immune system might
constitute amplifiers for the affinity maturation process of adaptive immunity46. Habitats of animals that are divided into multiple islands with a
central breeding location could potentially also act as amplifiers of selection. Our theory helps to identify those structures in natural settings.
Polygenic selection is likely to target some human traits, but the specific evolutionary mechanisms driving complex trait variation are largely unknown. We
developed an evolutionary compass for detecting selection and mutational bias that uses polarized GWAS summary
statistics from a single population. We found evidence for selection and mutational bias acting on variation in five traits (BMI, schizophrenia, Crohn’s disease, educational attainment, and height). We then used model-based analyses to show that these
signals can be explained by stabilizing selection with shifts in the fitness-phenotype relationship. We additionally provide evidence that selection has acted on
Neanderthal alleles for height, schizophrenia, and depression, and discuss potential sources of confounding. Our results provide a flexible and powerful framework for evolutionary analysis of complex phenotypes in
humans and other organisms, and provide insights into the evolutionary mechanisms driving variation in human polygenic traits.
Evolutionary medicine uses evolutionary theory to help elucidate why humans are vulnerable to disease and disorders. I discuss two different types of
evolutionary explanations that have been used to help understand human psychiatric disorders.
First, a consistent finding is that psychiatric disorders are moderately to highly heritable, and many, such as schizophrenia, are also highly disabling and
appear to decrease Darwinian fitness. Models used in evolutionary genetics to understand why genetic variation exists in fitness-related traits can be used to
understand why risk alleles for psychiatric disorders persist in the population. The usual explanation for species-typical adaptations—natural selection—is less
useful for understanding individual differences in genetic risk to disorders. Rather, two other types of models, mutation-selection-drift and balancing selection,
offer frameworks for understanding why genetic variation in risk to psychiatric (and other) disorders exists, and each makes predictions that are now testable
using whole-genome data.
Second, species-typical capacities to mount reactions to negative events are likely to have been crafted by natural selection to minimize fitness loss. The pain
reaction to tissue damage is almost certainly such an example, but it has been argued that the capacity to experience depressive symptoms such as sadness,
anhedonia, crying, and fatigue in the face of adverse life situations may have been crafted by natural selection as well. I review the rationale and strength of
evidence for this hypothesis.
Evolutionary hypotheses of psychiatric disorders are important not only for offering explanations for why psychiatric disorders exist, but also for generating
new, testable hypotheses and understanding how best to design studies and analyze data.
Understanding the quantitative genetics of crops has been and will continue to be central to maintaining and improving global food security. We outline four
stages that plant breeding either has already achieved or will probably soon achieve. Top-of-the-line breeding programs are currently in Breeding 3.0, where
inexpensive, genome-wide data coupled with powerful algorithms allow us to start breeding on predicted instead of measured phenotypes. We focus on three major
questions that must be answered to move from current Breeding 3.0 practices to Breeding 4.0: (1) How do we adapt crops to better fit agricultural environments? (2)
What is the nature of the diversity upon which breeding can act? (3) How do we deal with deleterious variants? Answering these questions and then translating them
to actual gains for farmers will be a significant part of achieving global food security in the twenty-first century.
The first decade of ancient genomics has revolutionized the study of human prehistory and evolution. We review new insights based on prehistoric modern human
genomes, including greatly increased resolution of the timing and structure of the out-of-Africa expansion, the diversification of present-day non-African
populations, and the earliest expansions of those populations into Eurasia and America. Prehistoric genomes now document population transformations on every
inhabited continent—in particular the effect of agricultural expansions in Africa, Europe, and Oceania—and record a history of natural selection that shapes
present-day phenotypic diversity. Despite these advances, much remains unknown, in particular about the genomic histories of Asia (the most populous continent) and
Africa (the continent that contains the most genetic diversity). Ancient genomes from these and other regions, integrated with a growing understanding of the
genomic basis of human phenotypic diversity, will be in focus during the next decade of research in the field.
Ethnicity looks something like kinship on a larger scale. The same math can be used to measure genetic similarity within ethnic/racial groups and relatedness
within families. For example, members of the same continental race are about as related (r = 0.18–0.26) as half-siblings (r = 0.25).
However (contrary to some claims) the theory of kin selection does not apply
straightforwardly to ethnicity, because inclusive fitness calculations based on Hamilton’s rule break down when there are complicated social interactions within groups, and/or groups are large and long-lasting. A more
promising approach is a theory of ethnic group selection, a special case of
cultural group selection. An elementary model shows that the genetic assimilation of a socially enforced cultural regime can promote group solidarity and lead to
the regulation of recruitment to groups, and to altruism between groups, based on genetic similarity—in short, to ethnic nepotism.
Several lines of evidence, from historical population genetics and political psychology, are relevant here.
[Keywords: kin selection, ethnicity, ethnocentrism, cultural group selection]
Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving
treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We
report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel
associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate
causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong
selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of
mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population.
In the three decades since the first predictive genetic tests became available, a great deal of data has accumulated to show how people respond to knowing
previously unknowable things. The rise of genetic testing has presented scientists with a 30-year experiment that has yielded some surprising insights into human
behavior. The data suggest that the vast majority react in ways that at first seem counterintuitive, or at least flout what experts predicted. But as genetic
testing becomes more widespread, the irrational behavior of a frightened few might start to look like the rational behavior of an enlightened majority. Doctors’
repeatedly failed attempts to anticipate people’s responses to genetic testing is not for want of preparation. Starting in the 1980s, they conducted surveys in
which they asked how people might approach the test, were one available. They noted the answers and planned accordingly. The trouble was, when the test became a
reality, their respondents didn’t do what they had said they would.
…In those preparatory surveys, roughly 70% of those at risk of Huntington’s said they would take a test if it existed. In fact, only around 15% do—a proportion
that has proved stable across countries and decades. A similar pattern emerged when tests became available for other incurable brain diseases…Prenatal genetic
testing is widely available, but the uptake by expecting couples in which one partner is a known carrier of an incurable disease is even lower than that of testing
among at-risk adults. Most opt to have a child whose risk of developing that disease is the same as theirs was at birth. Why do people act in this seemingly
irresponsible way with respect to their offspring?
A unique longitudinal study published in 2016
by Hanane Bouchghoul and colleagues at the Pitié-Salpêtrière Hospital in Paris unpacks that decision-making process. They interviewed 54 women—either
Huntington’s carriers or wives of carriers—and found that if a couple received a favorable result in a first prenatal test, the majority had the child and stopped
there. Most of those who got an unfavorable result terminated the pregnancy and tried again. If a second prenatal test produced a “good” result, they had the child
and stopped. But if it produced a “bad” result and another termination, most changed strategy. Some opted for preimplantation genetic diagnosis, removing the need
for termination, since only mutation-free embryos are implanted. Some abandoned the idea of having a child altogether. But nearly half, 45%, conceived naturally
again, and this time they did not seek prenatal testing. Summarizing the findings, the geneticist on the team, Alexandra Dürr, says, “The desire to have a child
overrides all else.”
…In a study that has yet to be published, Tibben has corroborated the French group’s conclusion. He followed 13 couples who, following counseling but prior to
taking a prenatal test, agreed they would terminate in the case of an unfavorable result. None of them did so when they got that result. “That means there are 13
children alive in the Netherlands today, whom we can be 100% sure are [Huntington’s] carriers”, he says.
Recent work has hinted at the linkage
disequilibrium (LD)-dependent architecture of human complex traits, where SNPs
with low levels of LD(LLD) have larger per-SNP heritability. Here we analyzed
summary statistics from 56 complex traits (average n = 101,401) by extending stratified LD score regression
to continuous annotations. We determined that SNPs with low LLD have
statistically-significantlylarger per-SNP heritability and that roughly half of this effect canbe
explained by functional annotations negatively correlated with LLD,such as DNase I hypersensitivity sites
(DHSs). The remaining signal is largely driven by our finding that more recent common variants tend to have lower
LLD and to explain more heritability (p = 2.38 × 10−104); the youngest 20% of common
SNPs explain 3.9× more heritability than the oldest 20%, consistent with the action of negative selection. We also
inferred jointly statistically-significant effects of other LD-related annotations and confirmed via forward simulations
that they jointly predict deleterious effects.
Selection alters human genetic variation, but the evolutionary mechanisms shaping complex traits and the extent of selection’s impact on polygenic trait
evolution remain largely unknown. Here, we develop a novel polygenic selection inference method (Polygenic Ancestral Selection Test Encompassing Linkage, or
PASTEL) relying on GWAS summary data from a single population. We use model-based
simulations of complex traits that incorporate human demography, stabilizing selection, and polygenic adaptation to show how shifts in the fitness landscape
generate distinct signals in GWAS summary data. Our test retains power for relatively ancient selection events and
controls for potential confounding from linkage disequilibrium. We apply
PASTEL to nine complex traits, and find evidence for selection acting on five of them (height, BMI, schizophrenia, Crohn’s disease, and educational attainment). This study provides evidence that selection modulates the
relationship between frequency and effect size of trait-altering alleles for a wide range of traits, and provides a flexible
framework for future investigations of selection on complex traits using GWAS data.
Background: The relationship between obesity and health expenditures is not well understood. We examined the relationship between genetic
predisposition to obesity measured by a polygenic risk score for body mass index (BMI) and Medicare
expenditures.
Methods: Biennial interview data from the Health and Retirement Survey for a nationally representative sample of older adults enrolled in
fee-for-service Medicare were obtained from 1991 through 2010 and linked to Medicare claims for the same period and to Genome-Wide Association Study
(GWAS) data. The study included 6,628 Medicare beneficiaries who provided 68,627 complete person-year observations
during the study period. Outcomes were total and service-specific Medicare expenditures and indicators for expenditures exceeding the 75th and
90thpercentiles. The BMI polygenic risk score wasderived from GWAS data. Regression models were used to examine how theBMI polygenic risk score was
related to health expenditures adjustingfor demographic factors and GWAS-derived ancestry.
Results: Greater genetic predisposition to obesity was associated with higher Medicare expenditures. Specifically, a 1 SD increase in the
BMI polygenic risk score was associated with a $805 (p < 0.001) increase in annual Medicare expenditures per
person in 2010 dollars (~15% increase), a $370 (p < 0.001) increase in inpatient expenses, and a $246 (p < 0.001) increase in outpatient
services. A 1 SD increase in the polygenic risk score was also related to increased likelihood of expenditures exceeding the 75th percentile by 18% (95%
CI: 10%–28%) and the 90th percentile by 27% (95% CI: 15%–40%).
Conclusion: Greater genetic predisposition to obesity is associated with higher Medicare expenditures.
The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another
3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental
ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of
involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry
pathogenic DNMs in coding sequences; approximatelyhalf of these DNMs disrupt
gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this
equates to almost 400,000 children born per year.
2017-adhikari.pdf: “The Genetic Diversity of the Americas”, Kaustubh Adhikari, Juan Camilo
Chacón-Duque, Javier Mendoza-Revilla, Macarena Fuentes-Guajardo, Andrés Ruiz-Linares, et al (2017-01-01)
Women choose younger and more highly educated sperm donors faster.
Education may be a proxy for resources even in the absence of paternal investment.
Behavioural research in reproductive medical settings is in its infancy.
The sperm donor market is a relevant and high stakes domain for behavioural research.
Reproductive medicine and commercial sperm banking have facilitated an evolutionary shift in how women are able to choose who fathers their offspring, by
notionally expanding women’s opportunity set beyond former constraints.
This study analyses 1546 individual reservations of semen by women from a private Australian assisted reproductive health facility across a 10 year period from
2006 to 2015. Using the time that each sample was available at the facility until reservation, we explore women’s preference for particular male
characteristics.
We find that younger donors, and those who hold a higher formal education compared to those with no academic qualifications are more quickly selected for
reservation by women. Both age and education as proxies for resources are at the centre of Parental Investment theory, and our findings further build on this
standard evolutionary construct in relation to female mate preferences.
Reproductive medicine not only provides women the opportunity to become a parent, where previously they would not have been able to, it also reveals that female
preference for resources of their potential mate (sperm donor) remain, even when the notion of paternal investment becomes redundant.
These findings build on behavioural science’s understanding of large-scale decisions and human behaviour in reproductive medical settings.
High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and
pathways.
To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used
~155,063 samples for independent replication.
We identified 30 new blood-pressure-associated or hypertension-associated genetic regions in the general population, including 3 rare missense variants in
RBM47, COL21A1 and RRAS with
larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a
low-frequency nonsense variant in ENPEP was identified.
Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of
hypertension and indicate new targets for clinical intervention.
Evolutionary forces that maintain genetic variance in traits can be inferred from their genetic architecture and fitness correlates.
A substantial amount of new data on the genomics and reproductive success associated with personality traits and intelligence has recently become
available.
Intelligence differences seem to have been selected for robustness against mutations.
Human tendencies to select, create and adapt to environments might support the maintenance of personality traits through balancing selection.
Like all human individual differences, personality traits and intelligence are substantially heritable. From an evolutionary perspective, this poses the
question what evolutionary forces maintain their genetic variation. Information about the genetic architecture and associations with evolutionary fitness permit
inferences about these evolutionary forces. As our understanding of the genomics of personality and its associations with reproductive success have grown
considerably in recent years, it is time to revisit this question. While mutations clearly affect the very low end of the intelligence continuum, individual
differences in the normal intelligence range seem to be surprisingly robust against mutations, suggesting that they might have been canalized to withstand such
perturbations. Most personality traits, by contrast, seem to be neither neutral to selection nor under consistent directional or stabilizing selection. Instead
evidence is in line with balancing selection acting on personality traits, probably supported by human tendencies to seek out, construct and adapt to fitting
environments.
The objective of this study was (1) to determine the impact of prenatal diagnosis (PND) forHuntington disease (HD) on subsequent reproductive choices and family structure;
and (2) to assess whether children born after PND were informed of their genetic status.
Out of 354 presymptomatic carriers of HD gene mutation, aged 18–45 years, 61 couples requested 101 PNDs. 54 women, 29
female carriers and 25 spouses of male carriers, accepted to be interviewed (0.6–16.3 years after the last PND,
median 6.5 years) on their obstetricalhistory and information given to children born after PND. Women werewilling to undergo 2 or more PNDs with a final success rate of 75%.
Reproductive decisions differed depending on the outcome of the first PND. If favourable, 62% couples decided against
another pregnancy and 10% chose to have an untested child. If unfavourable, 83% decided for another pregnancy (p < 0.01), and the majority (87%)
re-entered the PND procedure. In contrast, after a second PND, only 37% asked for
aPND and 30% chose to have an untested child. 33% had both, tested anduntested children. Among
children born after PND, 10 years and older, 75% were informed of their genetic status.
The decision to prevent transmission of the HD mutation is made anew with each pregnancy. Couples may need more psychological support after PND and pre-counselling sessions should take into account the effectof the outcome of a first PND on subsequent reproductive choices.
Samoans are a unique founder population with a high prevalence of obesity, making them well suited for identifying new genetic contributors to obesity. We
conducted a genome-wide association study (GWAS) in 3,072 Samoans, discovered a variant, rs12513649, stronglyassociated with body mass index (BMI) (p = 5.3 × 10(-14)), and replicated the association in 2,102
additional Samoans (p = 1.2 × 10−9). Targeted sequencing identified a strongly associated missense variant, rs373863828 (p.Arg457Gln), in
CREBRF (metap = 1.4 × 10(-20)). Although this variant is extremely rare in other populations, it is common in
Samoans (frequency of 0.259), with an effect size much larger than that of any other known common BMI risk variant
(1.36–1.45 kg/m(2) per copy of the risk-associated allele). In comparison to wild-type CREBRF, the Arg457Gln variant
when overexpressed selectively decreased energy use and increased fat storage in an adipocyte cell model. These data, in combination with evidence of
positive selection of the allele encoding p.Arg457Gln, support a ‘thrifty’ variant hypothesis as a factor in human obesity.
Because the worldwide demand for sperm donors is much higher than the actual supply available through fertility clinics, an informal online market has emerged
for sperm donation. Very little empirical evidence exists, however, on this newly formed market and even less on the characteristics that lead to donor success.
This article therefore explores the determinants of online sperm donors’ selection success, which leads to the production of offspring via informal donation. We
find that donor age and income play a statistically-significant role in donor success as measured by the number of times selected, even though there is no
requirement for ongoing paternal investment. Donors with less extroverted and lively personality traits who are more intellectual, shy and systematic are more
successful in realizing offspring via informal donation. These results contribute to both the economic literature on human behaviour and on large-scale
decision-making.
Across-nation differences in the mean values for complex traits are common1–8, but the reasons for these differences are unknown. Here we find that
many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416
individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size
estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic
variance for height and BMI, respectively, reflectpopulation genetic
differences. Population genetic divergence differed statistically-significantly from that in a null model (height, p < 3.94 × 10−8;
BMI,p < 5.95 × 10−4), and we find an among-population
genetic correlation for tall and slender individuals (r = −0.80, 95% CI = −0.95, −0.60), consistent with correlated selection for both phenotypes.
Observed differences in height among populations reflected the predicted genetic means (r = 0.51; p < 0.001), but environmental
differences across Europe masked genetic differentiation for BMI (p < 0.58).
Objective: To update and review the techniques and indications of preimplantation genetic diagnosis (PGD) and preimplantation geneticscreening (PGS).
Options: Discussion about the genetic and technical aspects of preimplantation reproductive techniques, particularly those using new
cytogenetic technologies and embryo-stage biopsy.
Outcomes: Clinical outcomes of reproductive techniques following the use of PGD and PGS are included. This update does not discuss in detail the adverse outcomes that have been recorded in association with assisted
reproductive technologies.
Evidence: Published literature was retrieved through searches of The Cochrane Library and MEDLINE in
April 2014 using appropriate controlled vocabulary (aneuploidy, blastocyst/physiology, genetic diseases, preimplantation diagnosis/methods,
fertilization in vitro) and key words (eg. preimplantation genetic diagnosis, preimplantation genetic screening, comprehensive chromosome screening,
aCGH, SNPmicroarray, qPCR, and embryo
selection). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies published from 1990 to
April 2014. There were no language restrictions. Searches were updated on a regular basis and incorporated in the update to January 2015. Additional
publications were identified from the bibliographies of retrieved articles. Grey (unpublished) literature was identified through searching the websites of health
technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international
medical specialty societies.
Values: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive
Health Care. (Table 1)
Benefits, harms, and costs: This update will educate readers about new preimplantation genetic concepts, directions, and technologies. The
major harms and costs identified are those of assisted reproductive technologies.
Summary: Preimplantation genetic diagnosis is an alternative to prenatal diagnosis for the detection of genetic disorders in couples at risk of
transmitting a genetic condition to their offspring. Preimplantation genetic screening is being proposed to improve the effectiveness of in vitro fertilization by
screening for embryonic aneuploidy. Though FISH-based PGS showed adverse effects on
IVF success, emerging evidence from new studies using comprehensive chromosome screening technology appears
promising.
Statistical methodology has played a key role in scientific animal breeding. Approximately one hundred years of statistical developments in animal breeding are
reviewed. Some of the scientific foundations of the field are discussed, and many milestones are examined from historical and critical perspectives. The review
concludes with a discussion of some future challenges and opportunities arising from the massive amount of data generated by livestock, plant, and human genome
projects.
Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with
other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes
enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes
underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional
olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory
system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic
cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse
models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in
the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from
random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a
resource for future disease mapping and phylogenomic studies across all members of the Felidae.
The domestication process leads to a change in behavioural traits, usually towards individuals that are less attentive to changes in their environment and less
aggressive. Empirical evidence for a difference in cognitive performance, however, is scarce. Recently, a functional linkage between an individual’s behaviour and
cognitive performance has been proposed in the framework of animal personalities via a shared risk-reward trade-off. Following this assumption, bolder and more
aggressive animals (usually the wild form) should learn faster. Differences in behaviour may arise during ontogeny due to individual experiences or represent
adaptations that occurred over the course of evolution. Both might singly or taken together account for differences in cognitive performance between wild and
domestic lineages. To test for such possible linkages, we compared wild cavies and domestic guinea pigs, both kept in a university stock for more than 30 years
under highly comparable conditions. Animals were tested in three behavioural tests as well as for initial and reversal learning performance. Guinea pigs were less
bold and aggressive than their wild congeners, but learnt an association faster. Additionally, the personality structure was altered during the domestication
process. The most likely explanation for these findings is that a shift in behavioural traits and their connectivity led to an altered cognitive performance. A
functional linkage between behavioural and cognitive traits seems to exist in the proposed way only under natural selection, but not in animals that have been
selected artificially over centuries.
Background: Assisted reproductive technologies (ART) such as invitro fertilisation
(IVF) and intracytoplasmic sperm injection (ICSI) bring together gametes outside of
the body to enhance the probability of fertilisation and pregnancy. Advanced sperm selection techniques are increasingly being employed in ART, most commonly in cyclesutilising ICSI. Advanced sperm selection techniques are
thought to improve the chance that structurally intact and mature sperm with high DNA integrity are selected for
fertilisation. Advanced sperm selection strategies include selection according to surface charge; sperm apoptosis; sperm birefringence; ability to bind to
hyaluronic acid; and sperm morphology under ultra-high magnification. These techniques theoretically improve ART
outcomes.
Objectives: To evaluate the impact of advanced sperm selection techniques on ART outcomes.
Search methods: Systematic search of electronic databases (Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the
Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing andAllied Health Literature (CINAHL), Latin American and Caribbean HealthScience Information Database (LILACS)),
trials registers (ClinicalTrials.gov, Current Controlled Trials, World Health Organization International Clinical
Trials Registry Platform), conference abstracts (Web of Knowledge) and grey literature (OpenGrey) for relevant randomised
controlled trials. We hand-searched the reference lists of included studies and similar reviews. The search was conducted in May 2014.
Selection criteria: We included randomised controlled trials (RCTs) comparing an advanced
sperm selection technique versus standard IVF or ICSI or versus another advanced
sperm selection technique. We excluded studies of sperm selection using ultra-high magnification (intracytoplasmic morphologically selected sperm
injection, or IMSI), as they are the subject of a separate Cochrane review. Quasi-randomised and pseudo-randomised
trials were excluded. Our primary outcome measure was live birth rate per woman randomly assigned. Secondary outcome measures included clinical pregnancy per woman
randomly assigned, miscarriage per clinical pregnancy and fetal abnormality per clinical pregnancy.
Data collection and analysis: Two review authors independently assessed eligibility of studies and risk of bias, and performed data extraction.
Disagreements were resolved by consultation with a third review author. Study investigators were consulted to resolve other queries that arose. Risk ratios (RRs)
were calculated with 95% confidence intervals (CIs). We planned to combine studies using a fixed-effect model, if sufficient data were available. The quality of
the evidence was evaluated using Grades of Recommendation, Assessment, Development and Evaluation (GRADE)
methods.
Main results: Two RCTs were included in the review. Both evaluated sperm selection
by hyaluronanic acid binding for ICSI, but only one reported live births. No studies were identified that were related
to surface charge selection, sperm apoptosis or sperm birefringence.
One RCTcompared hyaluronanic acid binding versus conventional ICSI. Live birth was not reported. Evidence was insufficient to show whether there was a difference between groups in clinical
pregnancy rates (RR 1.01, 95% CI 0.84 to 1.22, one RCT, 482 women). This evidence was deemed to be of
low quality, mainly as the result of poor reporting of methods and findings. Miscarriage data were unclear, and fetal abnormality rates were not reported.
The other RCT compared two different hyaluronanic acid binding techniques, SpermSlow and physiological
intracytoplasmic sperm injection (PISCI). Evidence was insufficient to indicate whether there was a difference
between groups in rates of live birth (RR 1.16, 95% CI 0.65 to 2.05, one RCT, 99 women), clinical
pregnancy (RR 1.07, 95% CI 0.67 to 1.71, one RCT, 99 women) or miscarriage (RR 0.76, 95% CI 0.24 to
2.44, one RCT, 41 women). The evidence for these comparisons was deemed to be of low quality, as it was
limited by imprecision and poor reporting of study methods. Fetal abnormality rates were not reported.
Authors’ conclusions: Evidence was insufficient to allow review authors to determine whether sperm selected by hyaluronanic acid binding
improve live birth or pregnancy outcomes in ART, and no clear data on adverse effects were available. Evidence was also
insufficient to show whether there is a difference in efficacy between the hyaluronic acid binding methods SpermSlow and PICSI. No randomised evidence evaluating sperm selection by sperm apoptosis, sperm birefringence or surface charge was found.
Further studies of suitable quality are required to evaluate whether any of these advanced sperm selection techniques can be recommended for use in clinical
practice.
The rich fossil record of equids has made them a model for evolutionary processes1. Here we present a 1.12× coverage draft genome from a horse bone
recovered from permafrost dated to approximately 560–780 thousand years before present (kyr BP)2,3. Our data represent the oldest full genome sequence
determined so far by almost an order of magnitude. For comparison, we sequenced the genome of a Late Pleistocene horse (43 kyr BP), and modern genomes of five
domestic horse breeds (Equus ferus caballus), a Przewalski’s horse (E. f. przewalskii) and a donkey (E. asinus). Our analyses suggest
that the Equus lineage giving rise to all contemporary horses, zebras and donkeys originated 4.0–4.5 million years before present (Myr BP), twice the
conventionally accepted time to the most recent common ancestor of the genus Equus4,5. We also find that horse population size fluctuated multiple times
over the past 2 Myr, particularly during periods of severe climatic changes. We estimate that the Przewalski’s and domestic horse populations diverged 38–72 kyr
BP, and find no evidence of recent admixture between the domestic horse breeds and the Przewalski’s horse investigated. This supports the contention that
Przewalski’s horses represent the last surviving wild horse population6. We find similar levels of genetic variation among Przewalski’s and domestic
populations, indicating that the former are genetically viable and worthy of conservation efforts. We also find evidence for continuous selection on the immune
system and olfaction throughout horse evolution. Finally, we identify 29 genomic regions among horse breeds that deviate from neutrality and show low levels of
genetic variation compared to the Przewalski’s horse. Such regions could correspond to loci selected early during domestication.
Whether China and the United States are destined to compete for domination in international politics is one of the major questions facing DoD. In a competition
with the People’s Republic of China, the United States must explore all of its advantages and all of the weaknesses of China that may provide an asymmetry for the
United States. This study examines one such asymmetry, the strategic consequences of Chinese racism. After having examined the literature on China extensively,
this author is not aware of a single study that addresses this important topic. This study explores the causes of Chinese racism, the strategic consequences of
Chinese racism, and how the United States may use this situation to advance its interests in international politics.
the study finds that xenophobia, racism, and ethnocentrism are caused by human evolution. These behaviors are not unique to the Chinese. However, they are
made worse by Chinese history and culture.
considers the Chinese conception of race in Chinese history and culture. It finds that Chinese religious-cultural and historical conceptions of race
reinforce Chinese racism. In Chinese history and contemporary culture, the Chinese are seen to be unique and superior to the rest of the world. Other peoples
and groups are seen to be inferior, with a sliding scale of inferiority. The major Chinese distinction is between degrees of barbarians, the “black devils”, or
savage inferiors, beyond any hope of interaction and the “white devils” or tame barbarians with whom the Chinese can interact. These beliefs are widespread in
Chinese society, and have been for its history…
evaluates the 9 strategic consequences of Chinese racism.
virulent racism and eugenics heavily inform Chinese perceptions of the world…
racism informs their view of the United States…
racism informs their view of international politics in three ways.
states are stable, and thus good for the Chinese, to the degree that they are unicultural.
Chinese ethnocentrism and racism drive their outlook to the rest of the world. Their expectation is of a tribute system where barbarians know that
the Chinese are superior.
there is a strong, implicit, racialist view of international politics that is alien and anathema to Western policy-makers and analysts. The Chinese
are comfortable using race to explain events and appealing to racist stereotypes to advance their interests. Most insidious is the Chinese belief that
Africans in particular need Chinese leadership.
the Chinese will make appeals to Third World states based on “racial solidarity”,…
Chinese racism retards their relations with the Third World…
Chinese racism, and the degree to which the Chinese permit their view of the United States to be informed by racism, has the potential to hinder China
in its competition with the United States because it contributes to their overconfidence…
as lamentable as it is, Chinese racism helps to make the Chinese a formidable adversary…
the Chinese are never going to go through a civil rights movement like the United States…
China’s treatment of Christians and ethnic minorities is poor…
considers the 5 major implications for United States decision-makers and asymmetries that may result from Chinese racism.
Chinese racism provides empirical evidence of how the Chinese will treat other international actors if China becomes dominant…
it allows the United States to undermine China in the Third World…
it permits a positive image of the United States to be advanced in contrast to China…
calling attention to Chinese racism allows political and ideological alliances of the United States to be strengthened…
United States defense decision-makers must recognize that racism is a cohesive force for the Chinese…
…The study’s fundamental conclusion is that endemic Chinese racism offers the United States a major asymmetry it may exploit with major countries, regions like
Africa, as well as with important opinion makers in international politics. The United States is on the right side of the struggle against racism and China is not.
The United States should call attention to this to aid its position in international politics.
This brief chapter first considers the theory of truncation selection on the mean, which is of general interest, and then examines a number of more specialized
topics that may be skipped by the casual reader. Truncation selection (Figure 14.1) occurs when all individuals on one side of a threshold
are chosen, and is by far the commonest form of artificial selection in breeding and laboratory experiments. One key result is that for a normally-distributed trait, the selection intensity
ī is fully determined by the fraction p saved (Equation 14.3a), provided that the chosen number of adults is large. This allows a breeder
or experimentalist to predict the expected response given their choice of p.
The remaining topics are loosely organized around the theme of selection intensity and threshold selection. First, when a small number of adults are chosen to
form the next generation, Equation 14.3a overestimates the expected ī, and we discuss how to correct for this small sample effect. This correction
is important when only a few individuals form the next generation, but is otherwise relatively minor. The rest of the chapter considers the response in discrete
traits. We start with a binary (present/absence) trait, and show how an underlying liability model can be used to predict response. We also examine binary trait
response in a logistic regression framework
(estimating the probability of showing the trait given some underlying liability scores) and the evolution of both the mean value on the liability scale and the
threshold value. We conclude with a few brief comments on response when a trait is better modeled as Poisson, rather than normally, distributed…In addition to
being the commonest form of artificial selection, truncation selection is also the most efficient, giving the largest selection intensity of any scheme culling the
same fraction of individuals from a population (Kimura & Crow 1978, Crow and Kimura 1979).
Profile of the development & launch of the SweeTango apple, a successor to Honeycrisp (via a hybridization with Zestar), developed by the University of Minnesota apple breeding program, which has been running since 1878 and created 27 notable apples
(earning its role as the state fruit).
Breeding programs like that are part of why Americans have historically shifted from consuming hard cider (made with inedible wild-types) to ‘eating apples’,
but progress was set back by a drastic decrease in variety to the McIntosh/Golden Delicious/Red Delicious triumvirate—Red Delicious degrading rapidly in quality. The apple revolution
began in the 1970s when Granny Smith proved US consumers would buy a better apple, and
was followed by the Fuji, Braeburn, and Gala.
How does one breed a new apple? Apples do not breed true and every offspring is wildly different. Apple breeders use brute force and brutally stringent
screening: an acre of thousands of saplings will be grown, and in all, the breeders will walk the row, grab 1 apple, chew it briefly, spit it out, and mark the
tree if good. Any sapling which is marked several years in a row (a few score out of thousands) survives; clones of it will be transplanted elsewhere for further
testing, and evaluated similarly for another decade. If and only a new apple tree & clones pass all these tests, will it even be considered for
commercialization.
“I’d like to give a tree a couple chances, but I just don’t have the mouth time for that”, Bedford explained. “So it’s one strike and you’re out. With all
these new trees coming on each year, you won’t have space unless you thin out the duds.” He sprayed another tree trunk with the mark of death. “But it is kind of
nerve-racking, because you want to give the tree a chance to do its best. No one wants to be known as the guy who killed the next Honeycrisp.”
The winner of such a process must be both brilliant and lucky, and Honeycrisp was both. But UMinn breeders watched with dismay as they felt the released
Honeycrisp saplings were mistreated or poorly-raised by careless commercial growers, and decided the next apple, SweeTango, would be a “clubapple”: it would be fully patented & controlled, and sold only to select apple growers who would be
required to follow stringent rules.
The “club apple” business model has proven to be its own revolution by internalizing the costs & benefits, incentivizing the creation of a dizzying variety of
new apples reaching the American grocery market every year.
Canine transmissible venereal tumor(CTVT) is an infectious cell line circulating in many feral dog populations. It originated once, about 10,000 years ago.
Phylogenetic analyses of mitochondrial sequences from dogs, wolves, and a geographically diverse collection of CTVT
samples indicate that the cancer has periodically acquired mitochondria from its host.
We suggest that this may be because the cancer’s own mitochondria have a tendency to degenerate, due to high mutation rates and relaxed selection, resulting in
host mitochondria being more fit.
[Review of modern apple breeding techniques: genome sequencing enables selecting on seeds rather than trees by predicting taste & robustness, saving years of
delay; this also allows avoiding the ‘GMO’ stigma by crossbreeding (quickly moving genes into new apple trees without direct
genetic editing using genomic selection), such as a “fast-flowering gene” to accelerate maturation during evaluation but then select it out for the final tree; the
creation of “The Gauntlet”, a greenhouse deliberately stocked with as many pathogens as possible, provides a stress test to weed out weak sapling as quickly as
possible; and buds can be cryogenically preserved to cut down storage costs by more than an order of magnitude.]
Until recently, geneticists, their skills honed on Arabidopsis and other quick-breeding flora, avoided fruit-tree research like a blight. Of the 11,000
U.S. field tests on plants with transgenic genes between 1987 and 2004, just 1% focused on fruit trees. That’s partly because of the slow pace. Whereas vegetables
like corn might produce two harvests each summer, apple trees need eons—around 5 years—to produce their first fruit, most of which will be disregarded as ugly,
bitter, or squishy. But everything in apple breeding is about to change. An Italian team plans to publish the decoded apple genome this summer, and scientists are
starting to single out complex genetic markers for taste and heartiness. In some cases the scientists even plan, by inserting genes from other species, to
eliminate the barren juvenile stage and push fruit trees to mature rapidly, greatly reducing generation times.
The effective size of a population, Ne,
determines the rate of change in the composition of a population caused by genetic
drift, which is the random sampling of genetic variants in a finite population. Ne is crucial in determining the level of variability in
a population, and the effectiveness of selection relative to drift.
There are 3 major ways by which the rate of genetic drift can be modelled in the simplest type of population: increase in variance of allele frequencies; approach to identity
by descent of all alleles; and coalescence of a sample of alleles into an
ancestral allele.
A general method for calculating Ne has been developed using coalescent theory for populations in which there are several ‘compartments’
(for example, ages or sexes) in the population from which alleles can be sampled. This involves the fast timescale approximation, in which the flow of alleles
between compartments is faster than the rate of coalescence.
Formulae are presented for the effects on Ne of differences in numbers of breeding males and females, differences in variance of
offspring number between males and females, levels of inbreeding, changes in population size and modes of inheritance.
Methods for estimating Ne for natural and artificial populations are described, using both demographic and genetic approaches. Examples
of the results of the application of these methods are presented.
The theory of how selection operates in a finite population is outlined, based on the formula for the probabilities of fixation of favourable and deleterious mutations. These depend on the
product of the selection coefficient and Ne.
There are data that show that the level of molecular sequence adaptation is reduced when Ne is low, as predicted from the product of the
selection coefficient and Ne.
The problem of describing neutral variability and the outcome of selection
in a spatially or genetically structured population is discussed. A great simplification occurs when there is a large number of local populations in a structured
metapopulation.
Data on molecular variation and evolution are described, which are consistent with these theoretical predictions.
The effective size of a population, Ne, determines the rate of change in the composition of a population caused by genetic drift, which is
the random sampling of genetic variants in a finite population. Ne is crucial in determining the level of variability in a population, and the
effectiveness of selection relative to drift. This article reviews the properties of Ne in a variety of different situations of biological
interest, and the factors that influence it. In particular, the action of selection means that Ne varies across the genome, and advances in
genomic techniques are giving new insights into how selection shapes Ne.
He rolled the dice again. This time, he was mimicking what he and his colleagues have been doing quietly around the globe for more than a half-century—using
radiation to scramble the genetic material in crops, a process that has produced valuable mutants like red grapefruit, disease-resistant cocoa and premium barley
for Scotch whiskey…The process leaves no residual radiation or other obvious marks of human intervention. It simply creates offspring that exhibit new
characteristics.
Though poorly known, radiation breeding has produced thousands of useful mutants and a sizable fraction of the world’s crops, Dr. Lagoda said, including
varieties of rice, wheat, barley, pears, peas, cotton, peppermint, sunflowers, peanuts, grapefruit, sesame, bananas, cassava and sorghum. The mutant wheat is used
for bread and pasta and the mutant barley for beer and fine whiskey.
The mutations can improve yield, quality, taste, size and resistance to disease and can help plants adapt to diverse climates and conditions…“Spontaneous
mutations are the motor of evolution”, Dr. Lagoda said. “We are mimicking nature in this. We’re concentrating time and space for the breeder so he can do the
job in his lifetime. We concentrate how often mutants appear—going through 10,000 to one million—to select just the right one.”
Radiation breeding is widely used in the developing world, thanks largely to the atomic agency’s efforts. Beneficiaries have included Bangladesh, Brazil, China,
Costa Rica, Egypt, Ghana, India, Indonesia, Japan, Kenya, Nigeria, Pakistan, Peru, Sri Lanka, Sudan, Thailand and Vietnam.
…Plant scientists say radiation breeding could play an important role in the future. By promoting crop flexibility, it could help feed billions of added mouths
despite shrinking land and water, rising oil and fertilizer costs, increasing soil exhaustion, growing resistance of insects to pesticides and looming climate
change. Globally, food prices are already rising fast.
“It’s not going to solve the world food crisis”, said J. Neil Rutger, former director of the Dale Bumpers National Rice Research Center in Stuttgart, Ark. “But
it will help. Modern plant breeders are using every tool they can get.”
The method was discovered some 80 years ago when Lewis J. Stadler of the University of Missouri used X-rays to zap barley seeds. The resulting plants were
white, yellow, pale yellow and some had white stripes—nothing of any practical value.
But the potential was clear. Soon, by exposing large numbers of seeds and young plants, scientists produced many more mutations and found a few hidden
beneficial ones. Peanuts got tougher hulls. Barley, oats and wheat got better yields. Black currants grew.
…In the 1950s and 1960s, the United States government promoted the method as part of its “atoms for peace” program and had notable successes. In 1960,
disease heavily damaged the bean crop in Michigan—except for a promising new variety that had been made by radiation breeding. It and its offspring quickly
replaced the old bean.
In the early 1970s, Dr. Rutger, then in Davis, Calif., fired gamma rays at rice. He and his colleagues found a semi-dwarf mutant that gave much higher
yields, partly because it produced more grain. Its short size also meant it fell over less often, reducing spoilage. Known as Calrose 76, it was released publicly
in 1976.
Today, Dr. Rutger said, about half the rice grown in California derives from this dwarf. Now retired in Woodland, Calif., he lives just a few miles from
where the descendants grow, he said.
A similar story unfolded in Texas. In 1929, farmers stumbled on the Ruby Red grapefruit, a natural mutant. Its flesh eventually faded to pink, however, and
scientists fired radiation to produce mutants of deeper color—Star Ruby, released in 1971, and Rio Red, released in 1985. The mutant offspring now account for
about 75% of all grapefruit grown in Texas.
Though the innovations began in the United States, the method is now used mostly overseas, with Asia and Europe the leading regions. Experts cited 2 main
reasons: domestic plant researchers over the decades have already made many, perhaps most of the easiest improvements that can be achieved with radiation, and they
now focus on highly popular fields like gene splicing.
“Most scientists here would say it’s pretty primitive”, Norman T. Uphoff, a professor of government and international agriculture at Cornell University, said of
the method. “It’s like being in a huge room with a flashlight.” But the flashlight is cheap, which has aided its international spread.
…Dr. Lagoda said a rust fungus threatened the Japanese pear, a pear with the crisp texture characteristic of apples. But one irradiated tree had a branch
that showed resistance. He said the Japanese cloned it, successfully started a new crop and with the financial rewards “paid for 30 years of research.”
The payoff was even bigger in Europe, where scientists fired gamma rays at barley to produce Golden Promise, a mutant variety with high yields and improved
malting. After its debut in 1967, brewers in Ireland and Britain made it into premium beer and whiskey. It still finds wide use. “The secret”, reads a recent
advertisement for a single malt Scotch whiskey costing $70.10$49.992007 a bottle, is “the continued use of finest Golden Promise barley and the insistence on oak sherry casks from
Spain.”
…Starting roughly a decade ago, for instance, the atomic agency helped scientists fight a virus that was killing cocoa trees in Ghana, which produces about 15%
of the world’s chocolate. The virus was killing and crippling millions of trees. In the city of Accra on the Atlantic coast, at the laboratories of the Ghana
Atomic Energy Commission, the scientists exposed cocoa plant buds to gamma rays. The mutants included one that endowed its offspring with better resistance to the
killer virus.
…The atomic agency had similar success in the Peruvian Andes, where some 3 million people live on subsistence farming. The region, nearly 2 miles high, has
extremely harsh weather. But 9 new varieties of barley improved harvests to the point that farmers had surplus crops to sell.
In 2006, Prof. Gomes Pando won the Peruvian prize for Good Government Practices for her work on the radiation mutants.
In Vietnam, the agency has worked closely with local scientists to improve production of rice, a crop that accounts for nearly 70% of the public’s food
energy.
One mutant had yields up to 3× higher than its parent and grew well in acidic and saline soils, allowing farmers to use it in coastal regions, including the
Mekong Delta.
Last year, a team of 10 Vietnamese scientists wrote in an agency journal, Plant Mutation Reports, that the nation had sown the new varieties across more than
one million hectares, or 3,860 square miles. The new varieties, they added, “have already produced remarkable economic and social impacts, contributing to poverty
alleviation in some provinces.”
Eggs and sperm are parallel bodily goods in that each contributes half of the reproductive material needed to create life. Yet these cells are produced by
differently sexed bodies, allowing for a comparative analysis of how the social process of bodily commodification varies based on sex and gender. Drawing on
interview and observational data from two egg agencies and two sperm banks in the United States, this article compares how staff recruit, screen, market, and
compensate women and men donors. Results show how gendered norms inspire more altruistic rhetoric in egg donation than in sperm donation, producing different
regimes of bodily commodification for women and men. I conclude by discussing the implications of these findings for debates in sociology of gender about
biological differences among women and men and the cultural norms attributed to these differences; debates in economic sociology about how social factors shape the
expansion of the market; and debates in medical sociology about the intersection of the market and medical practice.
In Japan, approximately 30% of dogs that enter training programs to become drug detection dogs successfully complete training. To clarify factors related to the
aptitude of drug detection dogs and develop an assessment tool, we evaluated genotypes and behavioural traits of 197 candidate dogs. The behavioural traits were
evaluated within 2 weeks from the start of training and included general activity, obedience training, concentration, affection
demand, aggression toward dogs, anxiety, and interest in target. Principal components analysis of these ratings yielded two
components: Desire for Work and Distractibility. Desire for Work was statistically-significantly related to successful completion of training (p <
0.001). Since 93.3% of dogs that passed training and 53.3% of the dogs that failed training had Desire for Work scores of 45 or higher, we will be able to reject
about half of inappropriate dogs before 3 months of training by adopting this cut-off point. We also surveyed eight polymorphic regions of four genes that have
been related to human personality dimensions. Genotypes were not related to whether dogs passed, but there was a weak relationship between Distractibility
and a 5HTThaplotype (p <
0.05).
A comprehensive evolutionary framework for understanding the maintenance of heritable behavioral variation in humans is yet to be developed. Some evolutionary
psychologists have argued that heritable variation will not be found in important, fitness-relevant characteristics because of the winnowing effect of natural
selection. This article propounds the opposite view. Heritable variation is ubiquitous in all species, and there are a number of frameworks for understanding its
persistence. The author argues that each of the Big Five dimensions of human personality can be seen as the result of a trade-off between different fitness costs
and benefits. As there is no unconditionally optimal value of these trade-offs, it is to be expected that genetic diversity will be retained in the population.
Our knowledge of Neanderthals is based on a limited number of remains and artifacts from which we must make inferences about their biology, behavior, and
relationship to ourselves. Here, we describe the characterization of these extinct hominids from a new perspective, based on the development of a Neanderthal
metagenomic library and its high-throughput sequencing and analysis. Several lines of evidence indicate that the 65,250 base pairs of hominid sequence so far
identified in the library are of Neanderthal origin, the strongest being the ascertainment of sequence identities between Neanderthal and chimpanzee at sites where
the human genomic sequence is different. These results enabled us to calculate the human-Neanderthal divergence time based on multiple randomly distributed
autosomal loci. Our analyses suggest that on average the Neanderthal genomic sequence we obtained and the reference human genome sequence share a most recent
common ancestor approximately 706,000 years ago, and that the human and Neanderthal ancestral populations split approximately 370,000 years ago, before the
emergence of anatomically modern humans. Our finding that the Neanderthal and human genomes are at least 99.5% identical led us to develop and successfully
implement a targeted method for recovering specific ancient DNA sequences from metagenomic libraries. This initial
analysis of the Neanderthal genome advances our understanding of the evolutionary relationship of Homo sapiens and Homo neanderthalensis and signifies the dawn of
Neanderthal genomics.
Evolutionary considerations suggest aging is caused not by active gene programming but by evolved limitations in somatic maintenance, resulting in a build-up of
damage. Ecological factors such as hazard rates and food availability influence the trade-offs between investing in growth, reproduction, and somatic survival,
explaining why species evolved different life spans and why aging rate can sometimes be altered, for example, by dietary restriction.
To understand the cell and molecular basis of aging is to unravel the multiplicity of mechanisms causing damage to accumulate and the complex array of systems
working to keep damage at bay.
Why Does Aging Occur?
Is Aging Programmed?
Evolutionary Genetics
Evolutionary Physiology
How Aging Is Caused
Molecular Mechanisms of Aging
Somatic Mutation Theory
Telomere Loss Theory
Mitochondrial Theory
Altered Proteins Theory and Waste Accumulation Theory
Network Theories of Aging
Cellular Aging
Modifying the Rate of Aging
Plasticity in the Natural Regulation of Aging Rate
Pushing the Boundaries of Our Understanding of Aging
Genomic information will increase selection efficiency in livestock. Genomics allows the tracing of transmission of genome fragments between generations, and
the location and identification of genes whose polymorphisms partially explain quantitative trait variability. This information is useful for a better evaluation
of the genetic values used by breeders, in particular when traits cannot be measured on a large scale for technical and/or economic reasons. It is also useful
for reducing the generation interval through an early choice of breeding animals, and for increasing selection intensity. The first applications with regard to
quality products and disease resistance are described in ruminant species. Interactions between genomic and reproductive biotechnologies are also described.
Preimplantation Genetic Diagnosis (PGD) is reviewed and novel fieldswhere it may be applied are
investigated. Technical advances of PGD in cattle embryos have already enabled its integration as a part of the
MOET (Multiple Ovulation Embryo Transfer) breeding system. PGD for
well-defined selection targets can enhance cattle breeding and embryo trade. It allows embryo selection according to their sex, and it may be used to breed special
cow lines, or top bulls, by selecting embryos for valuable production traits using Marker Assisted Selection (MAS). A good allelic profile and/or the insertion of a transgene can be detected by PGD.
This review article presents the technicalrequirements for PGD, and shows that this biotechnological method
has great economic potential.
Over the past two centuries, diseases have been separated into three categories: infectious diseases, genetic diseases, and diseases caused by too much or too
little of some noninfectious environmental constituent. At the end of the 19th century, the most rapid development was in the first of these categories;
within three decades after the first cause-effect linkage of a bacterium to a disease, most of the bacterial causes of common acute infectious diseases had been
identified. This rapid progress can be attributed in large part to Koch’s postulates, a rigorous systematic approach to identification of microbes as causes of
disease. Koch’s postulates were useful because they could generate conclusive evidence of infectious causation, particularly when (1) the causative organisms could
be isolated and experimentally transmitted, and (2) symptoms occurred soon after the onset of infection in a high proportion of infected individuals. While guiding
researchers down one path, however, the postulates directed them away from alternative paths: researchers attempting to document infectious causation were guided
away from diseases that had little chance of fulfilling the postulates, even though they might have been infectious. During the first half of the 20th
century, when the study of infectious agents was shifting from bacteria to viruses, Mendel’s genetics was being integrated into the study of disease. Some diseases
could not be ascribed to infectious causes using Koch’s postulates but could be shown to have genetic bases, particularly if they were inherited according to
Mendelian ratios. Mendel’s genetics and Koch’s postulates thus helped create a conceptual division of diseases into genetic and infectious categories, a division
that persists today.The third category—diseases resulting from noninfectious environmental causes—has a longer history. The known associations of poisons with
illness provided a basis for understanding physical agents as causes of disease. The apparent “contagiousness” of some chemical agents, such as the irritant of
poison ivy, led experts to consider that diseases could be contagious without being infectious. Even after the discovery of causative microbes during the last
quarter of the 19th century, many infectious diseases were considered contagious through the action of poisons, but not necessarily
infectious1.
…This tendency to dismiss infectious causation has occurred in spite of the recognition that (1) infectious diseases are typically influenced by both host
genetic and noninfectious environmental factors, and (2) some chronic diseases, such as tuberculosis and syphilis, have long been recognized as being caused by
infection. In this essay we analyze the present conceptions of disease etiology from an historical perspective and within the framework offered by evolutionary
biology. We begin by analyzing the degree to which infectious causation has been accepted for different categories of disease over the past two centuries with an
emphasis on (1) characteristics that make the infectious causes of different diseases conspicuous or cryptic, and (2) the need to detect ever more cryptic
infectious causes as a legacy of the more rapid recognition of the conspicuous infectious causes. We then consider principles and approaches that could facilitate
recognition of infectious diseases and other phenomena that are not normally considered to be of infectious origin.
The scientific literature on cat genetics contains a presumed typical example of natural selection affecting I
frequencies (long hair) in 16 Brazilian cat populations. It has been observed that the hotter and more tropical the climate
in Brazil, the lower the values of I frequencies in the cat populations.
Nevertheless, this study of some new cat populations in Latin America showed that all of them, independent of the
climate, had high or very high I frequencies.
I postulate that an alternative migrational-historical hypothesis exists that explains the correlation between the I frequencies and climate
characteristics (which are correlated with the latitude) without using natural selection explanations concerning the appearance of the I allele in
Brazil.
Serial passage experiments are a form of experimental evolution that is frequently used in applied sciences; for example, in vaccine development. During these
experiments, molecular and phenotypic evolution can be monitored in real time, providing insights into the causes and consequences of parasite evolution.
Within-host competition generally drives an increase in a parasite’s virulence in a new host, whereas the parasite becomes avirulent to its former host, indicating
a trade-off between parasite fitnesses on different hosts. Understanding why parasite virulence seldom escalates similarly in natural populations could help us to
manage virulence and deal with emerging diseases.
Figure 1: Response to selection. Mean apparent flying speeds of lines AA1 (■) and AA2 (●), measured every 5 generations.
The mean apparent flying speed of both lines increased from ~2 to 170 cm/sec and continued to respond at diminishing rates, without reaching a plateau, for
100 generations. Competitive fitness tests in generations 50 and 85 showed
minimal or no fitness loss in selected lines compared to controls. Sublines relaxed in generations 65 and 85 showed minimal or no regression in apparent flying
speed. Hybrid lines, from a cross of selected × control lines in generation 75, responded to reselection saltationally (Figure 5), showing that the chromosomes of the selected
lines had been assembled from alleles at many loci, from many different chromosomes in the base population.
Thus, major genetic change was achieved, but without the costs usually associated with strong directional selection. Large population size has been interpreted,
in opposing models, as either a brake or an accelerator in its effects on long-term change by selection. These results favor the second model, and challenge the
concept of rugged fitness surfaces underlying the first model.
This paper investigates the problem of how to conceive a robust theory of phenotypic adaptation in non-trivial models of evolutionary biology.
A particular effort is made to develop a foundation of this theory in the context of n-locus population
genetics. Therefore, the evolution of phenotypic traits is considered that are coded for by more than one gene. The potential for epistatic gene interactions is not a priori excluded. Furthermore, emphasis is laid on the
intricacies of frequency-dependent selection.
It is first discussed how strongly the scope for phenotypic adaptation is restricted by the complex nature of ‘reproduction mechanics’ in sexually reproducing
diploid populations. This discussion shows that one can easily lose the traces of Darwinism in n-locus models of population genetics.
In order to retrieve these traces, the outline of a new theory is given that I call ‘streetcar theory of evolution’. This theory is based on the same models
that geneticists have used in order to demonstrate substantial problems with the ‘adaptationist programme’. However, these models are now analyzed differently by
including thoughts about the evolutionary removal of genetic constraints. This requires consideration of a sufficiently wide range of potential mutant alleles and
careful examination of what to consider as a stable state of the evolutionary process. A particular notion of stability is introduced in order to describe
population states that are phenotypically stable against the effects of all mutant alleles that are to be expected in the long-run. Surprisingly, a long-term
stable state can be characterized at the phenotypic level as a fitness maximum, a Nash equilibrium or an ESS.
The paper presents these mathematical results and discusses—at unusual length for a mathematical journal—their fundamental role in our current understanding of
evolution.
When measures of individual differences are used to predict group performance, the reporting of correlations computed on samples of individuals invites
misinterpretation and dismissal of the data. In contrast, if regression equations, in which the correlations required are computed on bivariate means, as are the
distribution statistics, it is difficult to underappreciate or lightly dismiss the utility of psychological predictors.
Given sufficient sample size and linearity of regression, this technique produces cross-validated regression equations that forecast criterion means with almost
perfect accuracy. This level of accuracy is provided by correlations approaching unity between bivariate samples of predictor and criterion means, and this holds
true regardless of the magnitude of the “simple” correlation (eg. rxy = 0.20, or rxy = 0.80).
We illustrate this technique empirically using a measure of general intelligence as the predictor and other measures of individual differences and socioeconomic status as criteria. In addition to theoretical
applications pertaining to group trends, this methodology also has implications for applied problems aimed at developing policy in numerous fields.
…To summarize, psychological variables generating modest correlations frequently are discounted by those who focus on the magnitude of unaccounted for criterion
variance, large standard errors, and frequent false positive and false negative errors in predicting individuals. Dismissal of modest correlations (and the utility
of their regressions) by professionals based on this psychometric-statistical reasoning has spread to administrators, journalists, and legislative policy makers.
Some examples of this have been compiled by Dawes (1979, 1988) and Linn (1982). They range from squaring a correlation of 0.345 (ie., 0.12) and concluding that for
88% of students, “An SAT score will predict their grade rank no more accurately than a pair of dice”
(cf. Linn, 1982, p. 280) to evaluating the differential utility of two correlations 0.20 and 0.40 (based on different procedures for selecting graduate
students) as “twice of nothing is nothing” (cf. Dawes, 1979, p. 580).
…Tests are used, however, in ways other than the prediction of individuals or of a specific outcome for Johnny or Jane. And policy decisions based on tests
frequently have broader implications for individuals beyond those directly involved in the assessment and selection context (see the discussion later in this
article). For example, selection of personnel in education, business, industry, and the military focuses on the criterion performance of groups of applicants whose
scores on selection instruments differ. Selection psychologists have long made use of modest predictive correlations when the ratio of applicants to openings
becomes large. The relation of utility to size of correlation, relative to the selection ratio and base rate for success (if one ignores the test scores), is
incorporated in the well-known Taylor-Russell (1939) tables. These
tables are examples of how psychological tests have revealed convincingly economic and societal benefits (Hartigan & Wigdor 1989), even when a
correlation of modest size remains at center stage. For example, given a base rate of 30% for adequate performance and a predictive validity coefficient of 0.30
within the applicant population, selecting the top 20% on the predictor test will result in 46% of hires ultimately achieving adequate performance (a 16% gain over
base rate). To be sure, the prediction for individuals within any group is not strong—about 9% of the variance in job performance. Yet, when training is expensive
or time-consuming, this can result in huge savings. For analyses of groups composed of anonymous persons, however, there is a more unequivocal way of illustrating
the importance of modest correlations than even the Taylor-Russell tables provide.
Rationale for an Alternative Approach: Applied psychologists discovered decades ago that it is more advantageous to report correlations between
a continuous predictor and a dichotomous criterion graphically rather than as a number that varies between zero and one. For example, the correlation (point biserial) of about 0.40 with the pass-fail pilot training
criterion and an ability-stanine predictor looks quite impressive when graphed in the
manner of Figure 1a. In contrast, in Figure 1b, a scatter plot of a correlation of 0.40 between two continuous measures
looks at first glance like the pattern of birdshot on a target. It takes close scrutiny to perceive that the pattern in Figure 1b is not
quite circular for the small correlation. Figure 1a communicates the information more effectively than Figure 1b. When
the data on the predictive validity of the pilot ability-stanine were presented in the form of Figure 1a (rather than, say, as a scatter plot
of a correlation of 0.40; Figure 1b), general officers in recruitment, training, logistics, and operations immediately grasped the importance
of the data for their problems. Because the Army Air Forces were an attractive career choice, there were many more applicants for pilot training than could be
accommodated and selection was required…A small gain on a criterion for a unit of gain on the predictor, as long as it is predicted with near-perfect accuracy, can
have high utility.
Figure 1. a: Percentage of pilots eliminated from a training class as a function of pilot aptitude rating in stanines. Number of
trainees in each stanine is shown on each bar. (From DuBois 1947).
b: A synthetic example of a correlation of 0.40 (n = 400).
For some microorganisms, virulence may be an inadvertent consequence of mutation and
selection in the parasite population, occurring within a host during the course of an infection. This type of virulence is short-sighted, in that it engenders no advantage
to the pathogen beyond the afflicted host.
Few psychologists today are aware of the seminal role played by learning theorist Edward C. Tolman in the early development of the field of behavior genetics.
Tolman was the first to publish a study of selective breeding for maze-learning ability in rats. He continued to foster research in this field by supporting the
work of his students, particularly Robert C. Tryon. Tryon carried out the first major long-term study of maze-bright and maze-dull rats. This article focuses on
Tolman’s early years at Berkeley and the events culminating in the inheritance project, as well as on the evolution of this research under Tryon’s direction.
Young avian migrants of many species are able to find their species-specific or population-specific wintering area without the help of conspecifics. In
orientation tests hand-raised birds have been demonstrated to choose appropriate population-specific migratory directions, suggesting a genetic basis to this
behaviour.
I here report results of a cross-breeding experiment between individuals of 2 blackcap (Sylvia atricapilla) populations with widely different migratory directions. The orientation of the F1 offspring was intermediate between
and statistically-significantly different from that of both parental populations (Figure 2). The variance of individual mean directions in
the F1 generation did not increase compared with the parental groups, and the inheritance of migratory directions was not sex-linked.
The data provide direct evidence for a genetic basis of migratory directions in birds and demonstrate a phenotypically intermediate mode of inheritance.
Figure 2: Individual means of directional choices of hand-raised blackcaps during the early and late part of the autumn migration season.
Inner circle, parental generation; solid triangles, birds from the FRG ;open
triangles, birds from eastern Austria. Outer circles (full dots), F1 generation. Arrowheads, group mean directions. Compare
Table 1. Each symbol is based on an average of 8.1 orientation tests per bird in the parental generation (data from first and second
autumn of life combined) and 6.2 tests per bird and month in the F1 (first autumn only).
A new theory of attraction and liking based on kin selection suggests that people detect genetic similarity in others in order to give preferential treatment to
those who are most similar to themselves. There are many sources of empirical and theoretical support for this view, including (1) the inclusive fitness theory of
altruism, (2) kin recognition studies of animals raised apart, (3) assortative mating studies, (4) favoritism in families, (5) selective similarity among friends,
and (6) ethnocentrism. Specific tests of the theory show that (1) sexually interacting couples who produce a child are genetically more similar to each other in
blood antigens than they are either to sexually interacting couples who fail to produce a child or to randomly paired couples from the same sample; (2) similarity
between marriage partners is most marked in the more genetically influenced of sets of anthropometric, cognitive, and personality characteristics; (3) after the
death of a child, parental grief intensity is correlated with the child’s similarity to the parent; (4) long-term male friendship pairs are more similar to each
other in blood antigens than they are to random dyads from the same sample; and (5) similarity among best friends is most marked in the more genetically influenced
of sets of attitudinal, personality, and anthropometric characteristics. The mechanisms underlying these findings may constitute a biological substrate of
ethnocentrism, enabling group selection to occur.
The present paper aims to take a line that is somewhat more empirical than most of the previous theoretical work. Defining parasites broadly to include viruses,
bacteria, protozoans and helminths, we observe that the virulence of a parasite (the rate at which it induces host mortality) is usually coupled with the
transmission rate and with the time taken to recover by those hosts for whom the infection is not lethal. Specifically, in mice, men and other vertebrates (Fenner
& Ratcliffe, 1965; Burnet & White, 1972) and in many invertebrates (Maramorosch & Shope, 1975; Anderson & May, 1981) low virulence is generally associated with
effective immunological or non-specific responses which tend to suppress pathogen replication, with a concomitant reduction in transmissibility. Using data for the
epidemiological parameters characterizing the various grades of myxoma virusinfecting rabbits in Australia, we show how in this particular case virulence maybe expected
to evolve to an intermediate value; the analysis appears to accord with the observed facts. Other examples are discussed in a more qualitative way. In general,
we conclude that the complicated interplay between virulence and transmissibility of parasites leaves room for many coevolutionary paths to be followed, with many
endpoints.
Reverse and relaxed selection were carried out in sublines which were derived from 6 replicate lines of Drosophila during 86–89 generations of
selection for increased abdominal bristle number, and the reverse selection sublines were reciprocally crossed with selection lines of their origin.
The results of serial relaxed selection initiated at different generations of selection confirm that the accelerated responses observed in the selection lines
were largely due to deleterious genes, particularly lethals, with large effects on the selected character. The decline in mean bristle number under relaxed
selection was not much different between crowded and uncrowded relaxed sublines.
Reverse selection initiated at generation 57 was very effective, though it failed to bring the mean back to the base population level, and the genetic
differences between replicate sublines (two from each of the six lines) indicate that low bristle number genes were probably rare in the selection lines. The genes
which were still segregating after 57 generations of selection, on the average, did not show any directional dominance. The contribution of the X-chromosome to
selection response was proportional to its chromosome length.
[Keywords: long-term selection, relaxed selection, reverse selection, dominance of bristle number genes, Drosophila melanogaster]
The response to long-term selection for increased abdominal bristle number was studied in six replicate lines of Drosophila melanogaster derived from
the sc Canberra outbred strain. Each line was continued for 86–89 generations with 50 pairs of parents selected at an intensity of 20%, and subsequently
for 32–35 generations without selection. Response continued for at least 75 generations and average total response was in excess of 36 additive genetic standard
deviations of the base population (σA) or 51× the response in the first generation. The pattern of long-term response was diverse and
unpredictable typically with one or more accelerated responses in later generations. At termination of the selection, most of the replicate lines were extremely
unstable with high phenotypic variability, and lost much of their genetic gains rapidly upon relaxation of selection.
The variation in response among replicates rose in the early phase of selection to level off at approximately 7·6 σ[^2^~*A*~]{.supsub} around generation 25. As
some lines plateaued, it increased further to a level higher than would be accommodated by most genetic models. The replicate variation was even higher after many
generations of relaxed selection. The genetic diversity among replicates, as revealed in total response, the individuality of response patterns and variation of
the sex-dimorphism ratio, suggests that abdominal bristle number is influenced potentially by a large number of genes, but a smaller subset of them was responsible
for selection response in any one line.
5 replicate lines of D. melanogaster, which had been selected for increased abdominal bristle number for 58 or 69 generations, were pedigreed for 9
generations under selection with or without replacements for failed matings (SW and SO sublines) and under relaxed selection also with or without replacements (RW
and RO sublines).
Natural selection was effective in reducing mean bristle number in both RW and RO sublines (except in one line), but its opposition to artificial selection in
SW and SO sublines appeared to be only indirect. The relation between the two selective forces was inferred from their effects on effective population size, the
comparison of selection responses in SW and SO sublines, and the difference between expected and realized selection differentials.
Fertility was the most important factor affecting variance effective population size, while fecundity (with upper limits on the number of offspring scored) and
artificial selection were in most sublines similar in their relative importance. Measured by reduction in effective population size, the inbreeding effect of
artificial selection confined to the immediate generation was small (6.4%), but the cumulative effect estimated from the observed rate of inbreeding was quite
large (16%), tending to increase with more response.
The spread of genes from initial families seems to have been influenced by both artificial and natural selection. Correlations between the mean score of an
initial family and its genetic contribution indicate that additive genetic variance was still available at this stage of selection. The number of initial families
represented in SW and SO sublines was generally large even after nine generations, and few families made unusually large contributions.
Six replicate lines of Drosophila melanogaster, which had been selected for increased abdominal bristle number for more than 85 generations, were
assayed by hierarchical analysis of variance and offspring on parent regression immediately after selection ceased, and by single-generation realised heritability
after more than 25 generations of subsequent relaxed selection.
Half-sib estimates of heritability in 5 lines were as high as in the base population and much higher than observed genetic gains would suggest, excluding lack
of sufficient additive genetic variance as a cause of ineffective selection in these lines. Also, there was considerable diversity among the six lines in
composition of phenotypic variability: in addition to differences in the additive genetic component, one or more of the components due to dominance, epistasis,
sex-linkage or genotype-environment interaction appeared to be important in different lines.
Even after relaxed selection, single-generation realised heritabilities in four lines were as high as in the base population. As a large proportion of total
genetic gain must have been made by fixation of favourable alleles, the compensatory increase of genetic variability has been sought in a genetic model involving
genes at low initial frequencies, enhancement of gene effects during selection and/or new mutations.
Lethal frequencies on the second and third chromosomes were estimated 3 times in 6 replicate lines ofDrosophila melanogasterselected for increased
abdominal bristle number, at G 14–16, G 37–44 and G 79. Ten lethals were detected at a frequency of about 5% or higher at G 14–16, of which only one recurred in
subsequent tests. Another ten lethals which had not been detected previously were found at G 37–44, and the 5 most frequent ones recurred at G 79. In the last
test, 15 presumably new lethals were detected, of which at least 4 appeared well established. In addition, six reversions (from sc to sc⁺), a new
mutant at the scute locus and sca were discovered. The effects on the selected character of some lethals and visible mutants were large and variable, but
not always sufficient to explain the observed frequencies. The major lethals detected at G 37–44 and G 79 for the first time were most probably ‘mutations’ (in the
broad sense) which occurred during selection. The likely origins of such ‘mutations’ were discussed, with a suggestion that the known mutation rate for recessive
lethals would not be incompatible with the observed frequency of occurrence of the ‘mutations’.
In the first part of this two-part article (Nature
280, 361–367), mathematical models of directly transmitted microparasitic infections were developed, taking explicit account of the dynamics of the host
population. The discussion is now extended to both microparasites (viruses, bacteria and protozoa) and macroparasites (helminths and arthropods), transmitted
either directly or indirectly via one or more intermediate hosts. Consideration is given to the relation between the ecology and evolution of the transmission
processes and the overall dynamics, and to the mechanisms that can produce cyclic patterns, or multiple stable states, in the levels of infection in the host
population.
…This 2-part article has blended some new theoretical studies and new analysis of existing laboratory data with a review and synthesis of past and present
models for the overall transmission dynamics of parasitic infections. We have defined ‘parasite’ broadly to include viruses, bacteria and protozoans along with the
more conventional helminth and arthropod parasites, and we have concentrated attention upon the circumstances under which the infection may substantially alter the
growth rate of its host population.
Some of the theoretical conclusions can be pleasingly supported by hard data, while others remain more speculative. On the whole, our main goal is to help
elevate the study of host—parasite population dynamics to its proper place in ecological thinking: parasites (broadly defined) are probably at least as important
as the more usually-studied predators and insect parasitoids in regulating natural populations.
If the host population is taken to be a dynamic variable (rather than constant, as conventionally assumed), a wider understanding of the population biology of
infectious diseases emerges. In this first part of a two-part article, mathematical models are developed, shown to fit data from laboratory experiments, and used
to explore the evolutionary relations among transmission parameters. In the second part of the article, to be published in next week’s issue, the models are extended to include indirectly transmitted infections, and the
general implications for infectious diseases are considered.
…The effects of micro-parasitic infections on the dynamics of animal populations depend on the ecology of the interactions between host and parasite. These
patterns of disease behaviour involve 4 principal factors, namely: the host providing a habitat for the parasite; the degree to which the parasite induces host
mortality (or diminishes the reproductive capability of the host); the extent to which the host acquires immunity; and the necessity of transmission from one host
to the next. Overlaid on these factors are many biological complications, specific to individual host—parasite associations, whose sequential action is determined
by lifecycle structure.
In the second part of this article, we show how a common set of factors are involved in the dynamics of all infectious diseases, whether they are caused by
viral or helmintic agents, and whether they are transmitted directly or indirectly between hosts.
Social class and racial differences in human pair-bonding and heterosexual behavior patterns are considered in an evolutionary perspective. The expected
unpredictability of one’s future income stream should be an important parameter influencing these variables, according to theoretical considerations.
The literature is reviewed relevant to the prediction that those facing more predictable income streams should have a stronger marital pair bond and
premarital sexual activities more likely to lead to a strong pair bond, all other things being equal.
It is shown that those with high education or high occupational status do have more predictable income streams, and that their pair-bonding activities
exhibit the predicted consequences of that fact. A much smaller number of studies comparing different races’ sexual patterns are also consistent with the theory.
In the extremely few cases that permit it, it is found that a correlate of income predictability is more important in determining the dependent variables than
either race or class, as expected.
Alternative explanations of the data are briefly examined and found wanting, especially with respect to explaining the patterns of individuals whose parental
class differs from their own. Further research is suggested.
Within the context of a general discussion of the unintended effects of scientists on the results of their research, this work reported on the growing evidence
that the hypothesis of the behavioral scientist could come to serve as self-fulfilling prophecy, by means of subtle processes of communication between the
experimenter and the human or animal research subject. [The Science Citation Index (SCI) and the Social
Sciences Citation Index (SSCI) indicate that the book has been cited over 740 times since 1966 [as of 1979].]
—“Citation
Classic”
[Enlarged Edition, expanded with discussion of the Pygmalion effect etc: ISBN 0-470-01391-5]
The full data concerning the history of attenuated poliovirus strains developed by one of us (Sabin, 1965) for vaccine production do not appear in a single
journal. Over the past few years we have had frequent requests for the details such as isolation and attenuation and accordingly we felt that bringing the data
together in the report below would be both helpful and informative to those involved in the production and control of poliovirus vaccine (oral) prepared from these
strains.
Classic study of dog behavior, the authoritative information from 20 years of research at the Jackson Laboratory. The authors synthesize developmental problems
and canine genetics, based on study of 470 dogs. Central to the book is the role heredity plays in the development of behavior. Giving puppies an environment
designed on the principles of a well-run school, Scott and Fuller tested five breeds representing the major dog groups and carried out a Mendelian experiment with
two of the most different breeds: The basenji and the cocker spaniel. They found that heredity affects almost every trait tested; that gender affects
aggressiveness and the dominance order, but not trainability and problem-solving; that emotional traits profoundly influence performance; that, although breeds
differ widely in emotional and motivational characteristics, none shows distinct superiority in problem solving; and that detailed statistical analyses indicate a
highly complex pathway between primary gene action and its final effect on behavior. Includes important information on rearing methods, the origin and history of
dog breeds, basic behavior patterns and the psychological and behavioral development of puppies. Their careful scientific work demonstrated the importance and
existence of time limited phases in the early life of dogs within which certain experiences need to occur or the dogs may be forever deficient. Their work (with
that of Eckhard Hess’s on ducks and geese) demonstrated that these critical or sensitive periods in early development could be scientifically studied in ways
compatible with a scientific psychology. This book will always be especially valuable to dog breeders and trainers; its last chapters summarize in very clear terms
the particular phases in early development and experiences the dog needs to be adequately socialized. The reader can refer back to earlier chapters to get more
information on how the experiments were conducted and the distribution of results. It answers questions on proper age that puppies can be separated from their
mothers, what experiences are important to provide at what age, etc. Originally published in 1965. [ISBN:
0-226-74335-7]
The paper presents a theory of selection limits in artificial
selection. It is, however, developed primarily in terms of single genes.
For a single gene with selective advantage s, the chance of fixation (the expected gene frequency at the limit) is a function only of Ns, where N is the effective population size. In artificial selection based on individual
measurements, where the selection differential is ī standard deviations, the expected Limit of individual selection in any population is a function only
of Nī.
For low values of Nī, the total advance by selection is, for additive genes, 2N× the gain in the first generation but may be much greater
than this for recessives, particularly if their initial frequency is low.
The half-life of any selection process will, for additive genes, not be greater than 1.4N generations but may for rare recessives equal
2N.
The effect of an initial period of selection or inbreeding or of both together on the limits in further selection is discussed. It appears that the effects
of restrictions in population size on the selection limit may be a useful diagnostic tool in the laboratory.
The treatment can be extended to deal with the limits of further selection after the crossing of replicate lines from the same population when the initial
response has ceased.
In a selection programme of individual selection of equal intensity in both sexes, the furthest limit should be attained when half the population is selected
from each generation.
The treatment can also be extended to include selection based on progeny or family records.
Consideration of the optimum structure, as far as the limit is concerned, shows that the use of the information on relatives is always a sacrifice on the
eventual limit for the sake of immediate gain in the early generations. The loss may, however, be small in large populations.
The study of experimental epidemics recently reported by Greenwood, Hill, Topley and Wilson1 involves observations extending over some fifteen years and the use
of between 100,000 and 200,000 mice. Their methods were adequately controlled and ably presented. In fact, so carefully was their technic developed that it usually
proved possible to maintain herds of mice for months or years without the accidental introduction of any extraneous infection.
In one series of observations, six different epidemics of pasteurellosis were
under simultaneous observation. In the long continued epidemics under these experimental conditions, no tendency for periods of high or low mortality to recur at
definite seasons of the year was noted. Uncontaminated animals were introduced to many of their herds of infected mice at stated intervals. The great majority of
such mice were infected shortly after entrance, so that the reacting system at any moment contained a relatively small proportion of animals presenting a virgin
soil. After the first wave of disease and death that always follows the aggregation of an infected herd, the epidemics settled into a state of unstable
equilibrium. With a small number of daily uninfected immigrants, the mortality curves tended to show relatively wide and relatively regular fluctuations.
1936-greenwood-experimentalepidemiology.pdf: “Experimental Epidemiology”, M. Greenwood, A. Bradford Hill, W. W.
C. Topley, J. Wilson (1936-01-01):
The studies outlined in the report above have been in progress for some 15 years and they form an attempt to place the science of epidemiology on an
experimental basis. They are laborious and costly and the authors justify both the labour and the expense involved in the introduction. Although it is well known
that animal hosts and their microbial parasites vary in resistance and infectivity respectively, and that many other factors play their part in the form which an
epidemic disease takes, when all the odd pieces of knowledge are added together the answer is only a working hypothesis and not a conclusion. In other words, the
many questions regarding epidemics can only be answered by finding out actually what happens in an infected herd, not by deducing what might happen from knowledge
of what occurs in individual hosts. The herd must be the universe of study.
The experiments on which the report is based have involved the use of between 100,000 and 200,000 mice, and a brief outline of the general methods of experiment
are given. It has been possible to maintain herds for months or years infected with bacterial parasites such as Salmonella typhimurium and Pasteurella muriseptica without any cross-infection and to watch the effect of
various methods of interference on the spread of infection. Experiments have also been made with herds infected with the virus disease ectromelia.
From statistical analyses of the results, it is concluded that in herds of mice living in close and continuous contact and subject to the continuous or
intermittent immigration of susceptibles, the disease will never normally die out. It might happen that the disease would become extinct but such an event would be
a mere accident of small numbers. The form of the mortality curve depends mainly upon the rate of immigration and the equilibrium between hosts and parasites is
fundamentally unstable and, when disturbed, the system tends to pass through a period of violent fluctuations before equilibrium is again established. The average
resistance of surviving mice increases with survival in the herd but never becomes absolute. The great majority eventually succumb to the reigning disease.
Selection, both by death of the more susceptible, and by natural immunization, plays a part in the increased resistance displayed by surviving mice, and the
latter is probably the more important. An infected herd is a highly complex system, consisting of mice suffering from a fatal infection, others in a state of
infection-equilibrium that ends in death or recovery at some later period, others undergoing natural immunization by an infection of slighter degree, and a small
minority not yet infected. The differences in the form which epidemics display are due to the state of equilibrium established in this complex system, which may be
shifting or temporarily stabilized.
The level of mortality in a herd, the proportion of immunizing to fatal infections, and the degree to which infection occurs, are largely determined by the
characters of the bacterial strain with which the epidemic is initiated. It is considered that virulence and infectivity may vary, a highly potent “epidemic”
strain possessing both these characters.
Apart from changes in the conditions of contact, the only important method of interfering with the normal course of events in the infected herds is artificial
immunization. It has not, however, under the conditions of these experiments, approached the successes recorded from the field. As with natural immunization, so
artificial immunization has appeared to be more effective against the virus disease (ectromelia) than against the bacterial disease (mouse typhoid). In no
case, however, is the immunity attained complete, the immunized mice eventually dying from the prevailing disease. Infection of immunized animals is common and in
ectromelia, and probably in the bacterial diseases, many of the immunized and infected mice are infective for normal animals. It is, therefore, unlikely
that, even if it were possible to devise a method of immunization more effective in lowering mortality than those employed by the authors, infection could be
eliminated from the herds and so render safe the admission of susceptible immigrants.
As stated in the preface: “the experimental epidemic affords a more natural, and more severe, method of testing the value of any prophylactic procedure than
assays carried out by more artificial tests on individual animals. It can never, of course, replace field observations made under completely natural conditions;
but it may well indicate possible solutions to many of the more important practical problems, and so direct the field epidemiologist along the most fruitful lines
of inquiry.”
