Annotated bibliography of files in the directory /docs/genetics/selection/.
2009-01-01–2021-04-07
in progress
certainty: log
importance: 0
Files
1930-fisher-thegeneticaltheoryofnaturalselection.pdf#page=1191936-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.”
1936-jama.pdf: “Experimental Epidemiology”, JAMA editors (1936-12-01):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.
1960-robertson.pdf: “A theory of limits in artificial selection”, A. Robertson (1960):(1) The paper presents a theory of selection limits in artificial selection. It is, however, developed primarily in terms of single genes. (2) 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
. (3) For low values of
Nī
, the total advance by selection is, for additive genes, 2
N
times the gain in the first generation but may be much greater than this for recessives, particularly if their initial frequency is low. (4) The half-life of any selection process will, for additive genes, not be greater than 1.4
N
generations but may for rare recessives equal 2
N
. (5) 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. (6) 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. (7) 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. (8) 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.
1973-sabin.pdf: “History of Sabin attenuated poliovirus oral live vaccine strains”, A. B. Sabin, L. R. Boulger (1973-01-01):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.
1974-dudley-seventygenerationsofselectionforoilandproteininmaize.pdf1979-anderson.pdf: “Population biology of infectious diseases: Part I”, Roy M. Anderson, Robert M. May (1979-08-01):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.
1979-may-2.pdf: “Population biology of infectious diseases: Part II”, Robert M. May, Roy M. Anderson (1979-08-01):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.
1980-yoo-2.pdf: “Long-term selection for a quantitative character in large replicate populations of Drosophila melanogaster: II. Lethals and visible mutants with large effects”, B. H. Yoo (1980):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’.
1980-yoo-3.pdf: “Long-term selection for a quantitative character in large replicate populations of Drosophila melanogaster: Part 3: The nature of residual genetic variability”, B. H. Yoo (1980):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. [See also: Yoo 1980a{#1980-yoo-1-responsetoselection-2}, Yoo 1980b{#1980-yoo-2-largeeffectsizes-2}, Yoo et al 1980d{#1980-yoo-3-quantitativeselection-2}, Yoo 1980e{#1980-yoo-5-inbreeding-2}.]
1980-yoo-4.pdf: “Long-term selection for a quantitative character in large replicate populations of Drosophila melanogaster: Part 4: Relaxed and reverse selection”, B. H. Yoo, F. W. Nicholas, K. A. Rathie (1980-05-01):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]
1980-yoo-5.pdf: “Long-Term Selection for a Quantitative Character in Large Replicate Populations of Drosophila Melanogaster. V. The Inbreeding Effect of Selection”, B. H. Yoo (1980):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.
1980-yoo.pdf: “Long-term selection for a quantitative character in large replicate populations of Drosophila melanogaster: 1. Response to selection”, B. H. Yoo (1980):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 times 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.
1982-anderson.pdf: “Coevolution of hosts and parasites”, R. M. Anderson, R. M. May (1982):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 virus infecting 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.
1991-georges.pdf: “Velogenetics, or the synergistic use of marker assisted selection and germ-line manipulation”, M. Georges, J.M. Massey (1991):Until recently, artificial selection has relied on the biometrical evaluation of individual breeding values from an animal’s own performance and from performance of its relatives. This biometrical strategy is based on relatively simple genetic premises, operating within a “black box”. Briefly, the majority of economically important traits are so-called complex or quantitative traits, meaning that the phenotype of an animal is determined by both environment and a large number of genes with individually small, additive effects. The proportion of the phenotypic variation observed in a given population that is genetic in nature is the heritability of the trait. Substantial genetic progress has been obtained using this approach. One of the powers of the biometrical approach is that it obviates the need for any detailed molecular knowledge of the underlying genes or Economic Trait Loci (ETL).
However, it is believed that the molecular identification of these BTLs should allow for an increased genetic response by affecting both time and accuracy of selection, through a procedure called Marker Assisted Selection (MAS) (1,2). Moreover, we propose to use a scheme that we call “velogenetics”, or the combined use of Marker Assisted Selection and germ-line manipulations aimed at shortening the generation interval of domestic species (especially cattle), which would allow the efficient introgression of mapped Economic Trait Loci between genetic backgrounds.
1992-innis.pdf: “Tolman and Tryon: Early research on the inheritance of the ability to learn”, N. K. Innis (1992):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.
1998-ebert.pdf: “Experimental Evolution of Parasites”, Dieter Ebert (1998-11-20):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.
1998-haley.pdf: “Strategies to Utilize Marker-Quantitative Trait Loci Associations”, C. S. Haley, P. M. Visscher (1998):Marker-assisted selection holds promise because genetic markers provide completely heritable traits that can be measured at any age in either sex and that are potentially correlated with traits of economic value. Theoretical and simulation studies show that the advantage of using marker-assisted selection can be substantial, particularly when marker information is used, because normal selection is less effective, for example, for sex-limited or carcass traits. Assessment of the available information and its most effective use is difficult, but approaches such as crossvalidation may help in this respect. Marker systems are now becoming available that allow the high density of markers required for close associations between marker loci and trait loci. Emerging technologies could allow large numbers of polymorphic sites to be identified, practically guaranteeing that markers will be available that are in complete association with any trait locus. Identifying which polymorphism out of many that is associated with any trait will remain problematic, but multiple-locus disequilibrium measures may allow performance to be associated with unique marker haplotypes. This type of approach, combined with cheap and high density markers, could allow a move from selection based on a combination of “infinitesimal” effects plus individual loci to effective total genomic selection. In such a unified model, each region of the genome would be given its appropriate weight in a breeding program. However, the collection of good quality trait information will remain central to the use of these technologies for the foreseeable future.
[Keywords: markers, breeding, quantitative trait loci, selection]
2000-cochran.pdf: “Infectious Causation of Disease: An Evolutionary Perspective”, Gregory M. Cochran, Paul W. Ewald, Kyle D. Cochran (2000-01-01):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 infectious [1].
…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.
2001-bodo.pdf: “Preimplantation genetic diagnosis in cattle: A review”, S. Bodó, B. Baranyai, E. Gócza, J. Dohy, M. Markkula (2001):Preimplantation Genetic Diagnosis (PGD) is reviewed and novel fields where 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 technical requirements for PGD, and shows that this biotechnological method has great economic potential. 2007-almeling.pdf: “Selling Genes, Selling Gender: Egg Agencies, Sperm Banks, and the Medical Market in Genetic Material”, Rene Almeling (2007-06-01):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.
2007-maejima.pdf: “Traits and genotypes may predict the successful training of drug detection dogs”, Masami Maejima, Miho Inoue-Murayama, Keiichi Tonosaki, Naoto Matsuura, Shota Kato, Yasuhiro Saito, Alexander Weiss, Yuichi Murayama, Shin'ichi Ito (2007):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 5HTT haplotype (p < 0.05).
2010-kean.pdf: “Besting Johnny Appleseed: With a few tricks, and a lot of patience, fruit geneticists are undoing the work of an American legend”, Sam Kean (Science) (2010-04-16):[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.
2013-anonymous-strategicconsequencesofchineseracism.pdf: “The Strategic Consequences of Chinese Racism: A Strategic Asymmetry for the United States”, Anonymous, Anonymous (2013-01-07):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.
2013-orlando.pdf: “Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse”, Ludovic Orlando, Aurélien Ginolhac, Guojie Zhang, Duane Froese, Anders Albrechtsen, Mathias Stiller, Mikkel Schubert, Enrico Cappellini, Bent Petersen, Ida Moltke, Philip L. F. Johnson, Matteo Fumagalli, Julia T. Vilstrup, Maanasa Raghavan, Thorfinn Korneliussen, Anna-Sapfo Malaspinas, Josef Vogt, Damian Szklarczyk, Christian D. Kelstrup, Jakob Vinther, Andrei Dolocan, Jesper Stenderup, Amhed M. V. Velazquez, James Cahill, Morten Rasmussen, Xiaoli Wang, Jiumeng Min, Grant D. Zazula, Andaine Seguin-Orlando, Cecilie Mortensen, Kim Magnussen, John F. Thompson, Jacobo Weinstock, Kristian Gregersen, Knut H. Røed, Véra Eisenmann, Carl J. Rubin, Donald C. Miller, Douglas F. Antczak, Mads F. Bertelsen, Søren Brunak, Khaled A. S. Al-Rasheid, Oliver Ryder, Leif Andersson, John Mundy, Anders Krogh, M. Thomas P. Gilbert, Kurt Kjær, Thomas Sicheritz-Ponten, Lars Juhl Jensen, Jesper V. Olsen, Michael Hofreiter, Rasmus Nielsen, Beth Shapiro, Jun Wang, Eske Willerslev (2013-06-26):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.
2013-walsh-book2-ch14-draft.pdf: “Chapter 14. Short-term Changes in the Mean: 2. Truncation and Threshold Selection [2013 draft]”, Michael Lynch, Bruce Walsh (2013):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 and Crow 1978, Crow and Kimura 1979). [Preprint chapter of Evolution and Selection of Quantitative Traits, Lynch and Walsh 2018]
2014-brust.pdf: “Domestication effects on behavioural traits and learning performance: comparing wild cavies to guinea pigs”, Vera Brust, Anja Guenther (2014-07-06):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.
2014-mcdowell.pdf: “Advanced sperm selection techniques for assisted reproduction (Review)”, S. McDowell, B. Kroon, E. Ford, Y. Hook, D. Glujovsky, A. Yazdani (2014):Background: Assisted reproductive technologies (ART) such as in vitro 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 cycles utilising 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 and Allied Health Literature (CINAHL), Latin American and Caribbean Health Science 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 RCT compared 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.
2014-montague.pdf: “Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication”, Michael J. Montague, Gang Li, Barbara Gandolfi, Razib Khan, Bronwen L. Aken, Steven M. J. Searle, Patrick Minx, LaDeana W. Hillier, Daniel C. Koboldt, Brian W. Davis, Carlos A. Driscoll, Christina S. Barr, Kevin Blackistone, Javier Quilez, Belen Lorente-Galdos, Tomas Marques-Bonet, Can Alkan, Gregg W. C. Thomas, Matthew W. Hahn, Marilyn Menotti-Raymond, Stephen J. O’Brien, Richard K. Wilson, Leslie A. Lyons, William J. Murphy, and Wesley C. Warren (2014-10-03):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.
2015-dahdouh.pdf: “Technical Update: Preimplantation Genetic Diagnosis and Screening”, Elias M. Dahdouh, Jacques Balayla, François Audibert (2015-05):Objective: To update and review the techniques and indications of preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (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 (e.g., preimplantation genetic diagnosis, preimplantation genetic screening, comprehensive chromosome screening, aCGH, SNP microarray, 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. [Keywords: Preimplantation genetic diagnosis, preimplantation genetic screening, comprehensive chromosome screening, aCGH, SNP microarray, qPCR, embryo selection]
2015-gianola.pdf: “One Hundred Years of Statistical Developments in Animal Breeding”, Daniel Gianola, Guilherme J.M. Rosa (2014-11-03):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.
2015-robinson.pdf: “Population genetic differentiation of height and body mass index across Europe”, Matthew R. Robinson, Gibran Hemani, Carolina Medina-Gomez, Massimo Mezzavilla, Tonu Esko, Konstantin Shakhbazov, Joseph E. Powell, Anna Vinkhuyzen, Sonja I. Berndt, Stefan Gustafsson, Anne E. Justice, Bratati Kahali, Adam E. Locke, Tune H. Pers, Sailaja Vedantam, Andrew R. Wood, Wouter van Rheenen, Ole A. Andreassen, Paolo Gasparini, Andres Metspalu, Leonard H. van den Berg, Jan H. Veldink, Fernando Rivadeneira, Thomas M. Werge, Goncalo R. Abecasis, Dorret I. Boomsma, Daniel I. Chasman, Eco J. C. de Geus, Timothy M. Frayling, Joel N. Hirschhorn, Jouke Jan Hottenga, Erik Ingelsson, Ruth J. F. Loos, Patrik K. E. Magnusson, Nicholas G. Martin, Grant W. Montgomery, Kari E. North, Nancy L. Pedersen, Timothy D. Spector, Elizabeth K. Speliotes, Michael E. Goddard, Jian Yang, Peter M. Visscher (2015-09-14):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, reflect population 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).
2015-whyte.pdf: “Determinants of online sperm donor success: how women choose”, Stephen Whyte, Benno Torgler (2015-10-15):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. [Keywords: Online sperm donor market, informal market, offspring, donor success, personality traits]
2017-gazal.pdf: “Linkage disequilibrium-dependent architecture of human complex traits shows action of negative selection”, Steven Gazal, Hilary K. Finucane, Nicholas A. Furlotte, Po-Ru Loh, Pier Francesco Palamara, Xuanyao Liu, Armin Schoech, Brendan Bulik-Sullivan, Benjamin M. Neale, Alexander Gusev, Alkes L. Price (2017-09-11):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-significantly larger per-SNP heritability and that roughly half of this effect can be 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 times 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.
2017-kong.pdf: “Selection against variants in the genome associated with educational attainment”, Augustine Kong, Michael L. Frigge, Gudmar Thorleifsson, Hreinn Stefansson, Alexander I. Young, Florian Zink, Gudrun A. Jonsdottir, Aysu Okbay, Patrick Sulem, Gisli Masson, Daniel F. Gudbjartsson, Agnar Helgason, Gyda Bjornsdottir, Unnur Thorsteinsdottir, Kari Stefansson (2017-01-11):Epidemiological studies suggest that educational attainment is affected by genetic variants. Results from recent genetic studies allow us to construct a score from a person’s genotypes that captures a portion of this genetic component. Using data from Iceland that include a substantial fraction of the population we show that individuals with high scores tend to have fewer children, mainly because they have children later in life. Consequently, the average score has been decreasing over time in the population. The rate of decrease is small per generation but marked on an evolutionary timescale. Another important observation is that the association between the score and fertility remains highly statistically-significant after adjusting for the educational attainment of the individuals.
Epidemiological and genetic association studies show that genetics play an important role in the attainment of education. Here, we investigate the effect of this genetic component on the reproductive history of 109,120 Icelanders and the consequent impact on the gene pool over time. We show that an educational attainment polygenic score, POLYEDU, constructed from results of a recent study is associated with delayed reproduction (p < 10−100) and fewer children overall. The effect is stronger for women and remains highly statistically-significant after adjusting for educational attainment. Based on 129,808 Icelanders born between 1910 and 1990, we find that the average POLYEDU has been declining at a rate of ~0.010 standard units per decade, which is substantial on an evolutionary timescale. Most importantly, because POLYEDU only captures a fraction of the overall underlying genetic component the latter could be declining at a rate that is two to three times faster.
2017-mcrae.pdf: “Prevalence and architecture of de novo mutations in developmental disorders”, Jeremy F. McRae, Stephen Clayton, Tomas W. Fitzgerald, Joanna Kaplanis, Elena Prigmore, Diana Rajan, Alejandro Sifrim, Stuart Aitken, Nadia Akawi, Mohsan Alvi, Kirsty Ambridge, Daniel M. Barrett, Tanya Bayzetinova, Philip Jones, Wendy D. Jones, Daniel King, Netravathi Krishnappa, Laura E. Mason, Tarjinder Singh, Adrian R. Tivey, Munaza Ahmed, Uruj Anjum, Hayley Archer, Ruth Armstrong, Jana Awada, Meena Balasubramanian, Siddharth Banka, Diana Baralle, Angela Barnicoat, Paul Batstone, David Baty, Chris Bennett, Jonathan Berg, Birgitta Bernhard, A. Paul Bevan, Maria BitnerGlindzicz, Edward Blair, Moira Blyth, David Bohanna, Louise Bourdon, David Bourn, Lisa Bradley, Angela Brady, Simon Brent, Carole Brewer, Kate Brunstrom, David J. Bunyan, John Burn, Natalie Canham, Bruce Castle, Kate Chandler, Elena Chatzimichali, Deirdre Cilliers, Angus Clarke, Susan Clasper, Jill ClaytonSmith, Virginia Clowes, Andrea Coates, Trevor Cole, Irina Colgiu, Amanda Collins, Morag N. Collinson, Fiona Connell, Nicola Cooper, Helen Cox, Lara Cresswell, Gareth Cross, Yanick Crow, Mariella DAlessandro, Tabib Dabir, Rosemarie Davidson, Sally Davies, Dylan de Vries, John Dean, Charu Deshpande, Gemma Devlin, Abhijit Dixit, Angus Dobbie, Alan Donaldson, Dian Donnai, Deirdre Donnelly, Carina Donnelly, Angela Douglas, Sofia Douzgou, Alexis Duncan, Jacqueline Eason, Sian Ellard, Ian Ellis, Frances Elmslie, Karenza Evans, Sarah Everest, Tina Fendick, Richard Fisher, Frances Flinter, Nicola Foulds, Andrew Fry, Alan Fryer, Carol Gardiner, Lorraine Gaunt, Neeti Ghali, Richard Gibbons, Harinder Gill, Judith Goodship, David Goudie, Emma Gray, Andrew Green, Philip Greene, Lynn Greenhalgh, Susan Gribble, Rachel Harrison, Lucy Harrison, Victoria Harrison, Rose Hawkins, Liu He, Stephen Hellens, Alex Henderson, Sarah Hewitt, Lucy Hildyard, Emma Hobson, Simon Holden, Muriel Holder, Susan Holder, Georgina Hollingsworth, Tessa Homfray, Mervyn Humphreys, Jane Hurst, Ben Hutton, Stuart Ingram, Melita Irving, Lily Islam, Andrew Jackson, Joanna Jarvis, Lucy Jenkins, Diana Johnson, Elizabeth Jones, Dragana Josifova, Shelagh Joss, Beckie Kaemba, Sandra Kazembe, Rosemary Kelsell, Bronwyn Kerr, Helen Kingston, Usha Kini, Esther Kinning, Gail Kirby, Claire Kirk, Emma Kivuva, Alison Kraus, Dhavendra Kumar, V. K. Ajith Kumar, Katherine Lachlan, Wayne Lam, Anne Lampe, Caroline Langman, Melissa Lees, Derek Lim, Cheryl Longman, Gordon Lowther, Sally A. Lynch, Alex Magee, Eddy Maher, Alison Male, Sahar Mansour, Karen Marks, Katherine Martin, Una Maye, Emma McCann, Vivienne McConnell, Meriel McEntagart, Ruth McGowan, Kirsten McKay, Shane McKee, Dominic J. McMullan, Susan McNerlan, Catherine McWilliam, Sarju Mehta, Kay Metcalfe, Anna Middleton, Zosia Miedzybrodzka, Emma Miles, Shehla Mohammed, Tara Montgomery, David Moore, Sian Morgan, Jenny Morton, Hood Mugalaasi, Victoria Murday, Helen Murphy, Swati Naik, Andrea Nemeth, Louise Nevitt, Ruth NewburyEcob, Andrew Norman, Rosie OShea, Caroline Ogilvie, KaiRen Ong, SooMi Park, Michael J. Parker, Chirag Patel, Joan Paterson, Stewart Payne, Daniel Perrett, Julie Phipps, Daniela T. Pilz, Martin Pollard, Caroline Pottinger, Joanna Poulton, Norman Pratt, Katrina Prescott, Sue Price, Abigail Pridham, Annie Procter, Hellen Purnell, Oliver Quarrell, Nicola Ragge, Raheleh Rahbari, Josh Randall, Julia Rankin, Lucy Raymond, Debbie Rice, Leema Robert, Eileen Roberts, Jonathan Roberts, Paul Roberts, Gillian Roberts, Alison Ross, Elisabeth Rosser, Anand Saggar, Shalaka Samant, Julian Sampson, Richard Sandford, Ajoy Sarkar, Susann Schweiger, Richard Scott, Ingrid Scurr, Ann Selby, Anneke Seller, Cheryl Sequeira, Nora Shannon, Saba Sharif, Charles ShawSmith, Emma Shearing, Debbie Shears, Eamonn Sheridan, Ingrid Simonic, Roldan Singzon, Zara Skitt, Audrey Smith, Kath Smith, Sarah Smithson, Linda Sneddon, Miranda Splitt, Miranda Squires, Fiona Stewart, Helen Stewart, Volker Straub, Mohnish Suri, Vivienne Sutton, Ganesh Jawahar Swaminathan, Elizabeth Sweeney, Kate TattonBrown, Cat Taylor, Rohan Taylor, Mark Tein, I. Karen Temple, Jenny Thomson, Marc Tischkowitz, Susan Tomkins, Audrey Torokwa, Becky Treacy, Claire Turner, Peter Turnpenny, Carolyn Tysoe, Anthony Vandersteen, Vinod Varghese, Pradeep Vasudevan, Parthiban Vijayarangakannan, Julie Vogt, Emma Wakeling, Sarah Wallwark, Jonathon Waters, Astrid Weber, Diana Wellesley, Margo Whiteford, Sara Widaa, Sarah Wilcox, Emily Wilkinson, Denise Williams, Nicola Williams, Louise Wilson, Geoff Woods, Christopher Wragg, Michael Wright, Laura Yates, Michael Yau, Chris Nellker, Michael Parker, Helen V. Firth, Caroline F. Wright, David R. FitzPatrick, Jeffrey C. Barrett Matthew E. Hurles (2017-01-25):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; approximately half 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-wehby.pdf: “Genetic Predisposition to Obesity and Medicare Expenditures”, George L. Wehby, Benjamin W. Domingue, Fred Ullrich, and Fredric D. Wolinsky (2017-05-10):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 90th percentiles. The BMI polygenic risk score was derived from GWAS data. Regression models were used to examine how the BMI polygenic risk score was related to health expenditures adjusting for 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.
2017-wiggans.pdf: “Genomic Selection in Dairy Cattle: The USDA Experience”, George R. Wiggans, John B. Cole, Suzanne M. Hubbard, Tad S. Sonstegard (2017):Genomic selection has revolutionized dairy cattle breeding. Since 2000, assays have been developed to genotype large numbers of single-nucleotide polymorphisms (SNPs) at relatively low cost. The first commercial SNP genotyping chip was released with a set of 54,001 SNPs in December 2007. Over 15,000 genotypes were used to determine which SNPs should be used in genomic evaluation of US dairy cattle. Official USDA genomic evaluations were first released in January 2009 for Holsteins and Jerseys, in August 2009 for Brown Swiss, in April 2013 for Ayrshires, and in April 2016 for Guernseys. Producers have accepted genomic evaluations as accurate indications of a bull’s eventual daughter-based evaluation. The integration of DNA marker technology and genomics into the traditional evaluation system has doubled the rate of genetic progress for traits of economic importance, decreased generation interval, increased selection accuracy, reduced previous costs of progeny testing, and allowed identification of recessive lethals. [Keywords: genetic evaluation, single-nucleotide polymorphism, SNP, reliability, imputation, haplotype, genotype]
2018-collins.pdf: “The heritability of fertility makes world population stabilization unlikely in the foreseeable future”, Jason Collins, Lionel Page (2019):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]
2018-hendry.pdf: “The Contemporary Evolution of Fitness”, Andrew P. Hendry, Daniel J. Schoen, Matthew E. Wolak, Jane M. Reid (2018):The rate of evolution of population mean fitness informs how selection acting in contemporary populations can counteract environmental change and genetic degradation (mutation, gene flow, drift, recombination). This rate influences population increases (e.g., range expansion), population stability (e.g., cryptic eco-evolutionary dynamics), and population recovery (i.e., evolutionary rescue). We review approaches for estimating such rates, especially in wild populations. We then review empirical estimates derived from two approaches: mutation accumulation (MA) and additive genetic variance in fitness (IAw). MA studies inform how selection counters genetic degradation arising from deleterious mutations, typically generating estimates of <1% per generation. IAw studies provide an integrated prediction of proportional change per generation, nearly always generating estimates of <20% and, more typically, <10%. Overall, considerable, but not unlimited, evolutionary potential exists in populations facing detrimental environmental or genetic change. However, further studies with diverse methods and species are required for more robust and general insights.
2018-keller.pdf: “Evolutionary Perspectives on Genetic and Environmental Risk Factors for Psychiatric Disorders”, Matthew C. Keller (2018-05):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. [Keywords: evolution, psychiatric disorders, genetics, schizophrenia, depression]
2018-pardinas.pdf: “Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection”, Antonio F. Pardiñas, Peter Holmans, Andrew J. Pocklington, Valentina Escott-Price, Stephan Ripke, Noa Carrera, Sophie E. Legge, Sophie Bishop, Darren Cameron, Marian L. Hamshere, Jun Han, Leon Hubbard, Amy Lynham, Kiran Mantripragada, Elliott Rees, James H. MacCabe, Steven A. McCarroll, Bernhard T. Baune, Gerome Breen, Enda M. Byrne, Udo Dannlowski, Thalia C. Eley, Caroline Hayward, Nicholas G. Martin, Andrew M. McIntosh, Robert Plomin, David J. Porteous, Naomi R. Wray, Armando Caballero, Daniel H. Geschwind, Laura M. Huckins, Douglas M. Ruderfer, Enrique Santiago, Pamela Sklar, Eli A. Stahl, Hyejung Won, Esben Agerbo, Thomas D. Als, Ole A. Andreassen, Marie Bækvad-Hansen, Preben Bo Mortensen, Carsten Bøcker Pedersen, Anders D. Børglum, Jonas Bybjerg-Grauholm, Srdjan Djurovic, Naser Durmishi, Marianne Giørtz Pedersen, Vera Golimbet, Jakob Grove, David M. Hougaard, Manuel Mattheisen, Espen Molden, Ole Mors, Merete Nordentoft, Milica Pejovic-Milovancevic, Engilbert Sigurdsson, Teimuraz Silagadze, Christine Søholm Hansen, Kari Stefansson, Hreinn Stefansson, Stacy Steinberg, Sarah Tosato, Thomas Werge, GERAD1 Consortium, CRESTAR Consortium, David A. Collier, Dan Rujescu, George Kirov, Michael J. Owen, Michael C. O’Donovan and James T. R. Walters (2018):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.
2018-reeve.pdf: “A systematic review of the state of literature relating parental general cognitive ability and number of offspring”, Charlie L. Reeve, Michael D. Heeney, Michael A. Woodley of Menie (2018-11-01):Highlights:
- The relationship between general cognitive ability and reproduction is reviewed.
- There is an inverse relation between cognitive ability and number of children.
- The effect is stronger among females than males.
- The effect appears to be increasing in strength over time.
- Notable limitations of the current literature are reviewed.
The purpose of this study is to conduct a systematic review of the literature on the relationship between general cognitive ability and fertility among modern humans. Our goals were to (a) evaluate the state of the extant literature, and (b) provide a quantitative summary of effect sizes to the extent possible (given the limitations of the literature). A thorough search identified 17 unique datasets that passed the inclusion criteria. Using a Random Effects Model to evaluate the data, the overall weighted effect was r = −0.11, although the data also indicated a sex effect (stronger correlations among females than males), and a race effect (stronger correlations among Black and Hispanic populations compared to Whites). Importantly, the data suggest the correlation has been increasing in strength throughout the 20th century (and early 21st). Finally, we discovered several notable limitations of the extant literature; limitations that currently prohibit a psychometric meta-analysis. We discuss these issues with emphasis on improving future primary studies to allow for more effective meta-analytic investigations. [Keywords: intelligence, cognitive ability, g, reproductive success, meta-analysis, dysgenic trend]
2018-skoglund.pdf: “Ancient Human Genomics: The First Decade”, Pontus Skoglund, Iain Mathieson (2018):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.
2018-wallace.pdf: “On the Road to Breeding 4.0: Unraveling the Good, the Bad, and the Boring of Crop Quantitative Genomics”, Jason G. Wallace, Eli Rodgers-Melnick, Edward S. Buckler (2018):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: ( a) How do we adapt crops to better fit agricultural environments? ( b) What is the nature of the diversity upon which breeding can act? ( c) 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.
2019-baezortega.pdf: “Somatic evolution and global expansion of an ancient transmissible cancer lineage”, Adrian Baez-Ortega, Kevin Gori, Andrea Strakova, Janice L. Allen, Karen M. Allum, Leontine Bansse-Issa, Thinlay N. Bhutia, Jocelyn L. Bisson, Cristóbal Briceño, Artemio Castillo Domracheva, Anne M. Corrigan, Hugh R. Cran, Jane T. Crawford, Eric Davis, Karina F. de Castro, Andrigo B. de Nardi, Anna P. de Vos, Laura Delgadillo Keenan, Edward M. Donelan, Adela R. Espinoza Huerta, Ibikunle A. Faramade, Mohammed Fazil, Eleni Fotopoulou, Skye N. Fruean, Fanny Gallardo-Arrieta, Olga Glebova, Pagona G. Gouletsou, Rodrigo F. Häfelin Manrique, Joaquim J. G. P. Henriques, Rodrigo S. Horta, Natalia Ignatenko, Yaghouba Kane, Cathy King, Debbie Koenig, Ada Krupa, Steven J. Kruzeniski, Young-Mi Kwon, Marta Lanza-Perea, Mihran Lazyan, Adriana M. Lopez Quintana, Thibault Losfelt, Gabriele Marino, Simón Martínez Castañeda, Mayra F. Martínez-López, Michael Meyer, Edward J. Migneco, Berna Nakanwagi, Karter B. Neal, Winifred Neunzig, Máire Ní Leathlobhair, Sally J. Nixon, Antonio Ortega-Pacheco, Francisco Pedraza-Ordoñez, Maria C. Peleteiro, Katherine Polak, Ruth J. Pye, John F. Reece, Jose Rojas Gutierrez, Haleema Sadia, Sheila K. Schmeling, Olga Shamanova, Alan G. Sherlock, Maximilian Stammnitz, Audrey E. Steenland-Smit, Alla Svitich, Lester J. Tapia Martínez, Ismail Thoya Ngoka, Cristian G. Torres, Elizabeth M. Tudor, Mirjam G. van der Wel, Bogdan A. Viţălaru, Sevil A. Vural, Oliver Walkinton, Jinhong Wang, Alvaro S. Wehrle-Martinez, Sophie A. E. Widdowson, Michael R. Stratton, Ludmil B. Alexandrov, Iñigo Martincorena, Elizabeth P. Murchison (2019):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.
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, Kazumasa Wakamatsu, Jonathan S. Duke-Cohan, Jeffrey D. Jensen, Hopi E. Hoekstra (2019):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.
2019-bonner.pdf: “The evolution of evolution”, John T. Bonner (2019-12-01):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.
2019-chen-2.pdf: “Large-scale ruminant genome sequencing provides insights into their evolution and distinct traits”, Lei Chen, Qiang Qiu, Yu Jiang, Kun Wang, Zeshan Lin, Zhipeng Li, Faysal Bibi, Yongzhi Yang, Jinhuan Wang, Wenhui Nie, Weiting Su, Guichun Liu, Qiye Li, Weiwei Fu, Xiangyu Pan, Chang Liu, Jie Yang, Chenzhou Zhang, Yuan Yin, Yu Wang, Yue Zhao, Chen Zhang, Zhongkai Wang, Yanli Qin, Wei Liu, Bao Wang, Yandong Ren, Ru Zhang, Yan Zeng, Rute R. da Fonseca, Bin Wei, Ran Li, Wenting Wan, Ruoping Zhao, Wenbo Zhu, Yutao Wang, Shengchang Duan, Yun Gao, Yong E. Zhang, Chunyan Chen, Christina Hvilsom, Clinton W. Epps, Leona G. Chemnick, Yang Dong, Siavash Mirarab, Hans Redlef Siegismund, Oliver A. Ryder, M. Thomas P. Gilbert, Harris A. Lewin, Guojie Zhang, Rasmus Heller, Wen Wang (2019):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-delguidice.pdf: “Invisible Designers: Brain Evolution Through the Lens of Parasite Manipulation”, Marco Del Giudice (2019-09):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. [Keywords: behavior, brain evolution, hormones, neurobiology, parasite-host interactions, parasite manipulation.]
2019-hsieh.pdf: “Science Journals — AAAS”, PingHsun Hsieh, Mitchell R. Vollger, Vy Dang, David Porubsky, Carl Baker, Stuart Cantsilieris, Kendra Hoekzema, Alexandra P. Lewis, Katherine M. Munson, Melanie Sorensen, Zev N. Kronenberg, Shwetha Murali, Bradley J. Nelson, Giorgia Chiatante, Flavia Angela Maria Maggiolini, Hélène Blanché, Jason G. Underwood, Francesca Antonacci, Jean-François Deleuze, Evan E. Eichler (2019-10-18):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.
2019-immler.pdf: “Haploid Selection in “Diploid” Organisms”, Simone Immler (2019):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-karavani.pdf: “Screening Human Embryos for Polygenic Traits Has Limited Utility”, Ehud Karavani, Or Zuk, Danny Zeevi, Nir Barzilai, Nikos C. Stefanis, Alex Hatzimanolis, Nikolaos Smyrnis, Dimitrios Avramopoulos, Leonid Kruglyak, Gil Atzmon, Max Lam, Todd Lencz (2019-11-21):- 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.
2019-lopez.pdf: “Genomic Evidence for Local Adaptation of Hunter-Gatherers to the African Rainforest”, Marie Lopez, Jeremy Choin, Martin Sikora, Katherine Siddle, Christine Harmant, Helio A. Costa, Martin Silvert, Patrick Mouguiama-Daouda, Jean-Marie Hombert, Alain Froment, Sylvie Le Bomin, George H. Perry, Luis B. Barreiro, Carlos D. Bustamante, Paul Verdu, Etienne Patin, Lluís Quintana-Murci (2019-08-08):Highlights:
- 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. [Keywords: natural selection, genetic adaptation, rainforest, height, immunity, hunter-gatherers, admixture, Africa, positive selection, polygenic adaptation]
2019-reynolds.pdf: “Comparing signals of natural selection between three Indigenous North American populations”, Austin W. Reynolds, Jaime Mata-Míguez, Aida Miró-Herrans, Marcus Briggs-Cloud, Ana Sylestine, Francisco Barajas-Olmos, Humberto Garcia-Ortiz, Margarita Rzhetskaya, Lorena Orozco, Jennifer A. Raff, M. Geoffrey Hayes,, Deborah A. Bolnick (2019):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.
2019-sella.pdf: “Thinking About the Evolution of Complex Traits in the Era of Genome-Wide Association Studies”, Guy Sella, Nicholas H. Barton (2019-06-21):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 (i.e., of polygenic adaptation). Conversely, we ask how evolutionary thinking helps us to interpret findings from GWASs and informs related efforts of practical importance. [Keywords: evolution, genome-wide association study, GWAS, quantitative genetics, complex traits, polygenic adaptation, genetic architecture]
2019-therkildsen.pdf: “Contrasting genomic shifts underlie parallel phenotypic evolution in response to fishing”, Nina O. Therkildsen, Aryn P. Wilder, David O. Conover, Stephan B. Munch, Hannes Baumann, Stephen R. Palumbi (2019):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.
2019-trumble.pdf: “The Exposome in Human Evolution: From Dust to Diesel”, Benjamin C. Trumble, Caleb E. Finch (2019-12):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 six 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 preindustrial Homo 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.]
2019-zheng.pdf: “Cryptic genetic variation accelerates evolution by opening access to diverse adaptive peaks”, Jia Zheng, Joshua L. Payne, Andreas Wagner (2019):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.
2019-zhou.pdf: “Genetic architecture and adaptations of Nunavik Inuit”, Sirui Zhou, Pingxing Xie, Amélie Quoibion, Amirthagowri Ambalavanan, Alexandre Dionne-Laporte, Dan Spiegelman, Cynthia V. Bourassa, Lan Xiong, Patrick A. Dion, Guy A. Rouleau (2019):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).
2020-borrenpohl.pdf: “The value of early-stage phenotyping for wheat breeding in the age of genomic selection”, Daniel Borrenpohl, Mao Huang, Eric Olson, Clay Sneller (2020-06-01):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.
Abstract: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 times greater gain from selection. We conclude that GS can complement or replace phenotyping in early stages of phenotyping.
2020-chen.pdf: “Evidence of Polygenic Adaptation in Sardinia at Height-Associated Loci Ascertained from the Biobank Japan”, Minhui Chen, Carlo Sidore, Masato Akiyama, Kazuyoshi Ishigaki, Yoichiro Kamatani, David Schlessinger, Francesco Cucca, Yukinori Okada, Charleston W. K. Chiang (2020-06-12):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 of GWAS 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]
2020-derry.pdf: “Theory and Method: An Analysis of European and American Animal Breeding Practices, from the Eighteenth to the Twenty-First Century”, Margaret E. Derry (2020-07-01):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.
2020-hazel.pdf: “An age-dependent ovulatory strategy explains the evolution of dizygotic twinning in humans”, Wade N. Hazel, Robert Black, Richard C. Smock, Rebecca Sear, Joseph L. Tomkins (2020-05-11):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.
2020-hieber.pdf: “Inbreeding and Inbreeding Depression in Linebred Beef Cattle”, Jordan Hieber (2020-04):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 nucleotide polymorphisms, three strongly statistically-significant SNP within ROH, and some statistically-significant SNP within 12 previously identified genes. Identified for Line 1 were 50 ROH regions, 93 strongly statistically-significant SNP, three strongly statistically-significant SNP within ROH, and some statistically-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.
2020-kilbride.pdf: “In vitro fertilisation with preimplantation genetic testing: the need for expanded insurance coverage”, Madison K. Kilbride (2020-08-19):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 a technique 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.
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, Emil Jørsboe, Andrés Ingason, Mikkel W. Pedersen, Thorfinn Korneliussen, Helene Wilhelmson, Magdalena M. Buś, Peter Barros Damgaard, Rui Martiniano, Gabriel Renaud, Claude Bhérer, J. Víctor Moreno-Mayar, Anna K. Fotakis, Marie Allen, Raili Allmäe, Martyna Molak, Enrico Cappellini, Gabriele Scorrano, Hugh McColl, Alexandra Buzhilova, Allison Fox, Anders Albrechtsen, Berit Schütz, Birgitte Skar, Caroline Arcini, Ceri Falys, Charlotte Hedenstierna Jonson, Dariusz Błaszczyk, Denis Pezhemsky, Gordon Turner-Walker, Hildur Gestsdóttir, Inge Lundstrøm, Ingrid Gustin, Ingrid Mainland, Inna Potekhina, Italo M. Muntoni, Jade Cheng, Jesper Stenderup, Jilong Ma, Julie Gibson, Jüri Peets, Jörgen Gustafsson, Katrine H. Iversen, Linzi Simpson, Lisa Strand, Louise Loe, Maeve Sikora, Marek Florek, Maria Vretemark, Mark Redknap, Monika Bajka, Tamara Pushkina, Morten Søvsø, Natalia Grigoreva, Tom Christensen, Ole Kastholm, Otto Uldum, Pasquale Favia, Per Holck, Sabine Sten, Símun V. Arge, Sturla Ellingvåg, Vayacheslav Moiseyev, Wiesław Bogdanowicz, Yvonne Magnusson, Ludovic Orlando, Peter Pentz, Mads Dengsø Jessen, Anne Pedersen, Mark Collard, Daniel G. Bradley, Marie Louise Jørkov, Jette Arneborg, Niels Lynnerup, Neil Price, M. Thomas P. Gilbert, Morten E. Allentoft, Jan Bill, Søren M. Sindbæk, Lotte Hedeager, Kristian Kristiansen, Rasmus Nielsen, Thomas Werge, Eske Willerslev (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.
2020-moeinizade.pdf: “Multi-trait Genomic Selection Methods for Crop Improvement”, Saba Moeinizade, Aaron Kusmec, Guiping Hu, Lizhi Wang, Patrick S. Schnable (2020-06-01):Plant breeders make selection decisions based on multiple traits, such as yield, plant height, flowering time, and disease resistance. A commonly used approach in multi-trait genomic selection is index selection, which assigns weights to different traits relative to their economic importance. However, classical index selection only optimizes genetic gain in the next generation, requires some experimentation to find weights that lead to desired outcomes, and has difficulty optimizing non-linear breeding objectives. Multi-objective optimization has also been used to identify the Pareto frontier of selection decisions, which represents different trade-offs across multiple traits. We propose a new approach, which maximizes certain traits while keeping others within desirable ranges. Optimal selection decisions are made using a new version of the look-ahead selection algorithm, which was recently proposed for single trait genomic selection and achieved superior performance with respect to other state-of-the-art selection methods. To demonstrate the effectiveness of the new method a case study is developed using a realistic data set where our method is compared with conventional index selection. Results suggest that the multi-trait look-ahead selection is more effective at balancing multiple traits compared to index selection. [Keywords: multi-trait genomic selection, optimization, simulation]
2020-valge.pdf: “Natural selection on anthropometric traits of Estonian girls”, Markus Valge, Peeter Hõrak, Jonathan M. Henshaw (2020-07-22):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. [Keywords: body size, cranial volume, educational attainment, gene-culture coevolution, height, natural selection] 2020-wang.pdf: “Genome-wide selection and genetic improvement during modern maize breeding”, Baobao Wang, Zechuan Lin, Xin Li, Yongping Zhao, Binbin Zhao, Guangxia Wu, Xiaojing Ma, Hai Wang, Yurong Xie, Quanquan Li, Guangshu Song, Dexin Kong, Zhigang Zheng, Hongbin Wei, Rongxin Shen, Hong Wu, Cuixia Chen, Zhaodong Meng, Tianyu Wang, Yu Li, Xinhai Li, Yanhui Chen, Jinsheng Lai, Matthew B. Hufford, Jeffrey Ross-Ibarra, Hang He, Haiyang Wang (2020-04-27):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.
2020-winegard.pdf: “Coalitional Value Theory: an Evolutionary Approach to Understanding Culture”, Bo Winegard, Amanda Kirsch, Andrew Vonasch, Ben Winegard, David C. Geary (2020-05-08):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 (i.e., 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.
2021-bird.pdf: “No support for the hereditarian hypothesis of the Black-White achievement gap using polygenic scores and tests for divergent selection”, Kevin A. Bird (2021-02-02):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.
2021-durvasula.pdf: “Negative selection on complex traits limits phenotype prediction accuracy between populations”, Arun Durvasula, Kirk E. Lohmueller (2021-03-09):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]
2021-lenton.pdf: “Survival of the Systems”, Timothy M. Lenton, Timothy A. Kohler, Pablo A. Marquet, Richard A. Boyle, Michel Crucifix, David M. Wilkinson, Marten Scheffer (2021-01-04):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. [Keywords: selection, persistence, feedback cycle, ecosystem, social-ecological system]
2021-pereira.pdf: “African genetic diversity and adaptation inform a precision medicine agenda”, Luisa Pereira, Leon Mutesa, Paulina Tindana, Michele Ramsay (2021-01-11):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-vandervalk.pdf: “Million-year-old DNA sheds light on the genomic history of mammoths”, Tom van der Valk, Patrícia Pečnerová, David Díez-del-Molino, Anders Bergström, Jonas Oppenheimer, Stefanie Hartmann, Georgios Xenikoudakis, Jessica A. Thomas, Marianne Dehasque, Ekin Sağlıcan, Fatma Rabia Fidan, Ian Barnes, Shanlin Liu, Mehmet Somel, Peter D. Heintzman, Pavel Nikolskiy, Beth Shapiro, Pontus Skoglund, Michael Hofreiter, Adrian M. Lister, Anders Götherström, Love Dalén (2021-02-17):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 DNA should 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.
2021-wei.pdf: “A quantitative genomics map of rice provides genetic insights and guides breeding”, Xin Wei, Jie Qiu, Kaicheng Yong, Jiongjiong Fan, Qi Zhang, Hua Hua, Jie Liu, Qin Wang, Kenneth M. Olsen, Bin Han, Xuehui Huang (2021-02-01):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 genome navigation 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.