- “Invasion Genetics of the Longhorn Crazy Ant: the Global Expansion of a Double-clonal Reproduction System”, Tseng et al 2022
- “Virgin Birth: A Genetic Basis for Facultative Parthenogenesis”, Braun et al 2022
- “I Cloned My Dog—They Have Completely Different Personalities”, Spelliscy 2022
- “Continuous Cell-Free Replication and Evolution of Artificial Genomic DNA in a Compartmentalized Gene Expression System”, Okauchi & Ichihashi 2021
- “In a First, Surgeons Attached a Pig Kidney to a Human, and It Worked: A Kidney Grown in a Genetically Altered Pig Functions Normally, Scientists Reported. The Procedure May Open the Door to a Renewable Source of Desperately Needed Organs”, Rabin 2021
- “China Officially Bans CRISPR Babies, Human Clones and Animal-human Hybrids”, News 2021
- “Meet Elizabeth Ann, the First Cloned Black-Footed Ferret: Her Birth Represents the First Cloning of an Endangered Species Native to North America, and May Bring Needed Genetic Diversity to the Species”, Imbler 2021
- “Eight Proteins Turn Mouse Stem Cells into Egglike Cells: The Identification of the Transcription Factors That Elicit Oocyte Growth Will Aid Reproductive Biology Research and Might Help Women With Fertility Issues, Scientists Say”, Yeager 2020
- “The Przewalski’s Horse Project”, Restore 2020
- “A Single Gene Causes Thelytokous Parthenogenesis, the Defining Feature of the Cape Honeybee Apis Mellifera Capensis”, Yagound et al 2020
- “CC, World’s First Cloned Cat, Turns 18 Years Old”, Katz 2020
- “The Transcriptional Legacy of Developmental Stochasticity”, Ballouz et al 2019
- “Amid Animal Cruelty Debate, 80% of South Korea’s Sniffer Dogs Are Cloned”, Tribune 2019
- “Dog Cloning For Special Forces: Breed All You Can Breed”, Branwen 2018
- “In Vitro Gametogenesis and Reproductive Cloning: Can We Allow One While Banning the Other?”, Segers et al 2018
- “The Promise of Dog Cloning”, Oh et al 2018
- “Birth of Clones of the World’s First Cloned Dog”, Kim et al 2017
- “Propagation of Elite Rescue Dogs by Somatic Cell Nuclear Transfer”, Oh et al 2016
- “One Hundred Years of Statistical Developments in Animal Breeding”, Gianola & Rosa 2014
- “Behavioral Analysis of Cloned Puppies Derived from an Elite Drug-Detection Dog”, Choi et al 2014
- “Whole Genome Comparison of Donor and Cloned Dogs”, Kim et al 2013
- “Crunch: Building a Better Apple”, Seabrook 2011
- “Useful Mutants, Bred With Radiation”, Broad 2007
- “Traits and Genotypes May Predict the Successful Training of Drug Detection Dogs”, Maejima et al 2007
- “A Science Fiction Writer of the Fifties”, Leithauser 2006
- “Interspecies Implantation and Mitochondria Fate of Panda-Rabbit Cloned Embryos”, Chen et al 2002
- “Applications of Index Selection”, Walsh & Lynch 1997
- “Theory of Index Selection”, Walsh & Lynch 1997
- Truncation selection
- Truncated normal distribution
- Telescoping generations
- Regression toward the mean
- Przewalski’s horse
- Nine-banded armadillo
- Matthew Meselson § Meselson effect
- Marbled crayfish
- Little Nicky (cat)
- Liability threshold model
- Liability-threshold model
- Indotyphlops braminus
- Hwang Woo-suk
- Human cloning
- Dolly (sheep)
- Clonally transmissible cancer
- CC (cat)
- Alki David
- Adolfo Cambiaso
“Invasion Genetics of the Longhorn Crazy Ant: the Global Expansion of a Double-clonal Reproduction System”, Tseng et al 2022
Reproduction mode represents a key determinant for success of biological invasion as it influences the genetic variation and evolutionary potential of introduced populations.
The world’s most widespread invasive ant, Paratrechina longicornis, was found to display an unusual double-clonal reproduction system, whereby both males and queens were produced clonally, while workers are produced sexually. Despite its worldwide distribution, the origin of this ant species and the prevalence of the double-clonal reproductive system across the ant’s geographic range remain unknown.
To retrace the evolutionary history of this global invasive species and its reproductive system, we examined genetic variation and characterized the mode of reproduction of P. longicornis sampled worldwide using both microsatellite genotyping and mitochondrial DNA sequencing approaches.
Analyses of global genetic variations indicate that the Indian subcontinent is a genetic diversity hotspot of this species, suggesting that this geographic area is at least part of its native range.
Our analyses revealed that inferred native and introduced populations both exhibit double-clonal reproduction. Remarkably, queens and males worldwide belong to two separate, non-recombining clonal lineages. Workers are highly heterozygous and first-generation inter-lineage hybrids, a pattern strongly supportive of a strict worldwide prevalence of double clonality. By maintaining heterozygosity in the worker force, this unusual genetic system allows P. longicornis to avoid inbreeding during colonization bottlenecks and may have acted as an adaptive trait linked to the species’’ invasion success.
“Virgin Birth: A genetic basis for facultative parthenogenesis”, (2022-03-14; ; similar):
Sexual reproduction evolved 1–2 billion years ago and underlies the biodiversity of our planet. Nevertheless, devolution of sexual into asexual reproduction can occur across all phyla of the animal kingdom. The genetic basis for how parthenogenesis can arise is completely unknown. To understand the mechanism and benefits of parthenogenesis, we have sequenced the genome of the facultative parthenogen, Drosophila mercatorum, and compared its organisation and expression pattern during parthenogenetic or sexual reproduction. We identified three genes, desat2, Myc, and polo in parthenogenetic D. mercatorum that when mis-regulated in a non-parthenogenetic species, D. melanogaster, enable facultative parthenogenetic reproduction. This simple genetic switch leads us to propose that sporadic facultative parthenogenesis could evolve as an 9escape route9 preserving the genetic lineage in the face of sexual isolation.
“I Cloned My Dog—They Have Completely Different Personalities”, (2022-01-30; ; ; similar):
Sydney’s always been a ball-crazy dog, too. From a very young age, she just loved chasing a ball. But it wasn’t until she was 6 years old that something really remarkable happened. I was taking her for a midnight walk on Granville Island in Vancouver when she smelt the scent of a ball underground and just went after it. She spent 30 minutes digging a hole and retrieved that ball. It dawned on me then that if I could replace the scent of a ball with a sulfide scent, we could train her to be a prospector.
…As a mineral prospecting company, we will typically visit a location after an aerial geophysical survey has taken place. A plane will have mapped the area and if that survey has shown some geophysical anomaly, something that could indicate a sulfidic mineral; say nickel, copper or gold, we will then hike through to investigate further. After I trained Sydney to detect sulfide scents, she would join us. If there is cover on the ground that obscures our view, she is able to detect any sulfidic minerals beneath. Provided it’s a reasonable depth of course, she can’t detect minerals buried 100 meters underground! Her method is to dig away at the ground, and then she’ll make a little nest on what she finds and go to sleep on it. She’s done her job at that stage and then she’s so happy she just has a nap. But it’s not like dogs hunting a scent across the countryside, it’s quite a calm procedure.
…very few dogs can detect mineral sulfides and report back on them in the way she can. We tried to see if Border Collies could do it, and they only could, but only to a degree. We then spent about 6 months with an Australian Cattle dog called Jake but he still didn’t have Sydney’s capability…Over the years we tried various other dogs but none had the capacity for detection that Sydney has.
…Then, in 2019, I discovered a place in Texas that clones pets, called ViaGen, and they were very easy to deal with. A local veterinarian completed a biopsy so we could provide tissue samples for the cloning process, those samples were sent to ViaGen for further processing and placed in storage until we pulled the trigger to clone Sydney in 2021. I have no real understanding of the specifics of the cloning process, other than what I had to be involved in and provide in terms of tissue samples, but I have always been an advocate for animal welfare locally and in Mexico. Cloning Sydney cost us $50,000 and we thought that meant we were getting one puppy in the fall of 2021. Then, on July 9, I got a call saying, “Your puppies have arrived.”
…Both [cloned puppies, Olivia and Fiona] are also completely ball crazy and very agile…I have found it takes around 400 training sessions, each around 15 minutes long, for a dog to develop confidence to hunt a particular scent, but our training is incredibly kind to the dogs and we see lack of praise as a punishment. Olivia and Fiona’s official training is in its early stages, but both show incredible aptitude for one or two scents related to copper, nickel, gold and diamond. They really do have Sydney’s instinct when it comes to scenting, but they go about it differently. My first indication of the puppies’ ability to detect scents happened with Fiona, I was leash training her with a harness when she was 100 days old. As we walked through the yard, she put on the brakes, started digging, and found a buried bone that was about 3 inches under the soil. She has been introduced to bones before, but she instinctively smelt this bone that had probably been buried there for more than a year.
People have different reactions to cloning, some think it’s OK and others think it’s wrong because there are so many dogs in shelters already. I can understand that perspective, but in our particular situation there really wasn’t any other option than to reproduce Sydney in the way we did…in my work circles, people know all about Sydney, so they are really enchanted by the puppies. Anyone familiar with Sydney is excited that there are 2 more of her around to continue her legacy of mineral detection.
“Continuous Cell-Free Replication and Evolution of Artificial Genomic DNA in a Compartmentalized Gene Expression System”, Okauchi & Ichihashi 2021
2021-okauchi.pdf: “Continuous Cell-Free Replication and Evolution of Artificial Genomic DNA in a Compartmentalized Gene Expression System”, (2021-11-15; ; similar):
In all living organisms, genomic DNA continuously replicates by the proteins encoded in itself and undergoes evolution through many generations of replication. This continuous replication coupled with gene expression and the resultant evolution are fundamental functions of living things, but they have not previously been reconstituted in cell-free systems.
In this study, we combined an artificial DNA replication scheme with a reconstituted gene expression system and microcompartmentalization to realize these functions. Circular DNA replicated through rolling-circle replication followed by homologous recombination catalyzed by the proteins, phi29 DNA polymerase, and Cre recombinase expressed from the DNA. We encapsulated the system in microscale water-in-oil droplets and performed serial dilution cycles. Isolated circular DNAs at Round 30 accumulated several common mutations, and the isolated DNA clones exhibited higher replication abilities than the original DNA due to its improved ability as a replication template, increased polymerase activity, and a reduced inhibitory effect of polymerization by the recombinase.
The artificial genomic DNA, which continuously replicates using self-encoded proteins and autonomously improves its sequence, provides an useful starting point for the development of more complex artificial cells.
[Keywords: DNA replication, cell-free synthetic biology, artificial cell, Darwinian evolution]
“In a First, Surgeons Attached a Pig Kidney to a Human, and It Worked: A Kidney Grown in a Genetically Altered Pig Functions Normally, Scientists Reported. The Procedure May Open the Door to a Renewable Source of Desperately Needed Organs”, Rabin 2021
“In a First, Surgeons Attached a Pig Kidney to a Human, and It Worked: A kidney grown in a genetically altered pig functions normally, scientists reported. The procedure may open the door to a renewable source of desperately needed organs”, (2021-10-10; ; similar):
So surgeons at N.Y.U. Langone Health took an astonishing step: With the family’s consent, they attached the pig’s kidney to a brain-dead patient who was kept alive on a ventilator, and then followed the body’s response while taking measures of the kidney’s function. It is the first operation of its kind. The researchers tracked the results for just 54 hours, and many questions remained to be answered about the long-term consequences of such an operation. The procedure will not be available to patients any time soon, as there are substantial medical and regulatory hurdles to overcome.
Still, experts in the field hailed the surgery as a milestone. “This is a huge breakthrough”, said Dr. Dorry Segev, a professor of transplant surgery at Johns Hopkins School of Medicine who was not involved in the research. “It’s a big, big deal.”
A steady supply of organs from pigs—which could eventually include hearts, lungs and livers—would offer a lifeline to the more than 100,000 Americans currently on transplant waiting lists, including the 90,240 who need a kidney. 12 people on the waiting lists die each day.
…The transplanted kidney was obtained from a pig genetically engineered to grow an organ unlikely to be rejected by the human body. In a close approximation of an actual transplant procedure, the kidney was attached to blood vessels in the patient’s upper leg, outside the abdomen. The organ started functioning normally, making urine and the waste product creatinine “almost immediately”, according to Dr. Robert Montgomery, the director of the N.Y.U. Langone Transplant Institute, who performed the procedure in September.
…The group was involved in the selection and identification of the brain-dead patient receiving the experimental procedure. The patient was a registered organ donor, and because the organs were not suitable for transplantation, the patient’s family agreed to permit research to test the experimental transplant procedure.
…The combination of 2 new technologies—gene editing and cloning—has yielded genetically altered pig organs. Pig hearts and kidneys have been transplanted successfully into monkeys and baboons, but safety concerns precluded their use in humans. “The field up to now has been stuck in the preclinical primate stage, because going from primate to living human is perceived as a big jump”, Dr. Montgomery said.
The kidney used in the new procedure was obtained by knocking out a pig gene that encodes a sugar molecule that elicits an aggressive human rejection response. The pig was genetically engineered by Revivicor and approved by the Food and Drug Administration for use as a source for human therapeutics.
Dr. Montgomery and his team also transplanted the pig’s thymus, a gland that is involved in the immune system, in an effort to ward off immune reactions to the kidney.
After attaching the kidney to blood vessels in the upper leg, the surgeons covered it with a protective shield so they could observe it and take tissue samples over the 54-hour study period. Urine and creatinine levels were normal, Dr. Montgomery and his colleagues found, and no signs of rejection were detected during more than 2 days of observation. “There didn’t seem to be any kind of incompatibility between the pig kidney and the human that would make it not work”, Dr. Montgomery said. “There wasn’t immediate rejection of the kidney.”
“China officially bans CRISPR babies, human clones and animal-human hybrids”, (2021-03-28; ; ; similar):
China’s new Criminal Code, which came into effect four weeks ago on March 1st, has a new section dedicated to ‘illegal medical practices’, which makes it a punishable crime to create gene-edited babies, human clones and animal-human chimeras.
The new section is an amendment to Article 336 of China’s Criminal Law, and officially outlaws “the implantation of genetically-edited or cloned human embryos into human or animal bodies, or the implantation of genetically edited or cloned animal embryos into human bodies”—with penalties ranging from fines to 7 years imprisonment.
…Although Dr He had been sentenced for genetically modifying human embryos, China’s previous criminal code on ‘illegal medical practices’, under which he was sentenced, was extremely vague on the gene-editing of human embryos, and was mostly used to prosecute providers of dangerous medical procedures, and not researchers. The only official Chinese Government legal document that made a stipulation against genetically altering human embryos at the time of Dr He’s sentencing was a scientifically-outdated 2003 guideline by the Chinese Ministry of Health, which mostly addressed ethical issues on human embryonic stem cell research. And thus due to this legal vagueness on human gene-editing, legal experts in China found the court sentencing of Dr He to be very problematic…The new addition to the criminal code is meant to clear up these questions.
“Meet Elizabeth Ann, the First Cloned Black-Footed Ferret: Her Birth Represents the First Cloning of an Endangered Species Native to North America, and May Bring Needed Genetic Diversity to the Species”, Imbler 2021
“Meet Elizabeth Ann, the First Cloned Black-Footed Ferret: Her birth represents the first cloning of an endangered species native to North America, and may bring needed genetic diversity to the species”, (2021-02-18; ; similar):
Her successful cloning is the culmination of a years-long collaboration with the U.S. Fish and Wildlife Service, Revive & Restore, the for-profit company ViaGen Pets & Equine, San Diego Zoo Global and the Association of Zoos and Aquariums.
Cloned siblings are on the way, and potential (cloned) mates are already being lined up. If successful, the project could bring needed genetic diversity to the endangered species. And it marks another promising advance in the wider effort to use cloning to retrieve an ever-growing number of species from the brink of extinction…“Pinch me”, joked Oliver Ryder, the director of conservation genetics at San Diego Zoo Global, over a Zoom call. “The cells of this animal banked in 1988 have become an animal.”
…In 2013, the Fish and Wildlife Service approached Revive & Restore to explore how biotechnology, which the nonprofit develops in pursuit of the de-extinction of species, could help increase the genetic diversity of black-footed ferrets. The following year, Revive & Restore sequenced the genomes of four black-footed ferrets. First there was Balboa, who was born by means of artificial insemination using cryopreserved, genetically diverse sperm. Second was Cheerio, who was born naturally and shares ancestry from all seven founders; Novak calls him an “every ferret.” The last two ferrets came from tissue samples at the Frozen Zoo, one male called “Studbook Number 2” and one female named Willa. “When we looked at Balboa, we saw from an empirical standpoint that a great deal of genetic diversity had been rescued by reaching back into the past”, Mr. Novak said.
Revive & Restore designed a proposal and submitted it to Fish and Wildlife. In 2018, the nonprofit received the first-ever permit to research cloning an endangered species. Revive & Restore partnered with the commercial cloning company ViaGen Pets & Equine to design the cloning process.
The first trial began around Halloween. The Frozen Zoo sent Willa’s cryogenically preserved cell line to ViaGen’s lab in New York. ViaGen created embryos and implanted them into a domestic ferret surrogate. At day 14, an ultrasound confirmed heartbeats. The surrogate was shipped to the conservation center and was watched 24 hours a day for signs of labor. On Dec. 10, Elizabeth Ann was delivered via C-section. “Our beautiful little clone”, Mr. Novak said. On Elizabeth Ann’s 65th day of life the technicians drew her blood, swabbed her cheek and sent the samples to Samantha Wisely, a conservation geneticist at the University of Florida, who confirmed that Elizabeth Ann was, in fact, a black-footed ferret.
…When the clones reach sexual maturity, they will breed, and then their offspring will be bred back with wild black-footed ferrets to ensure there is no mitochondrial DNA left over from the surrogate mother.
“Eight Proteins Turn Mouse Stem Cells into Egglike Cells: The Identification of the Transcription Factors That Elicit Oocyte Growth Will Aid Reproductive Biology Research and Might Help Women With Fertility Issues, Scientists Say”, Yeager 2020
“Eight Proteins Turn Mouse Stem Cells into Egglike Cells: The identification of the transcription factors that elicit oocyte growth will aid reproductive biology research and might help women with fertility issues, scientists say”, (2020-12-16; ; similar):
“This demonstrates that you can go directly from stem cells to oocytes. I think that is exciting”, Petra Hajkova, a developmental epigeneticist at Imperial College London who was not involved in the study, tells The Scientist. The work, she notes, will help researchers explore the basic biology of oocyte development. In the future, says study coauthor Nobuhiko Hamazaki of Kyushu University, the research could aid in cloning endangered animals or helping women with mitochondrial diseases to have healthy children.
…“It’s believed that oocytes develop from germ cells, but we could make oocytes from non-germ cells”, he explains. “At first, I was so surprised that I could not believe my results, so I repeated the experiment again and again and when I got the same results, I was finally convinced.”…“I was initially in complete disbelief to see mouse stem cells so quickly and easily take the form of oocytes based on introducing just a handful of factors, but repeated experiments proved it was true”, said Nobuhiko Hamazaki, PhD, first author on the study reporting the results and assistant professor at Kyushu University at the time of the research. “To find that eight transcription factors could lead to such big changes was quite astonishing.”
…Richard Schultz, a cell biologist at the University of California, Davis, who was not involved in the study, says the work to identify the core set of transcription factors that can drive embryonic stem cells into a state where they look like oocytes is impressive. But the egglike cells don’t undergo meiosis, so they are not functional. “It’s a big step, but only 95% there. We haven’t gotten 100% there” to understanding the factors essential for maturation of germline egg cells to oocytes and then to viable eggs with half their chromosomes. Despite not working out the pathway to meiosis, the work “enabled us to produce a large number of oocytes. We believe that this technology can accelerate basic biological research on oocytes, which are still one of the most mysterious cell types”, Hamazaki says. He explains that the work could improve animal cloning because of the vast number of oocytes produced by the team’s technique…“Cytoplasm from oocytes is an invaluable resource in reproductive biology and medicine, and this method could provide a novel tool for producing large amounts of it without any invasive procedures”, commented Hayashi. “While the processes could still be much more complex for humans, these initial results in mice are very promising.”
The world’s first successfully cloned endangered Przewalski’s horse (Equus przewalskii) was born on August 6, 2020. Revive & Restore, San Diego Zoo Global (SDZG), and ViaGen Equine collaborated to clone from a cell line of a genetically important stallion that had been cryopreserved since 1980 at the SDZG Frozen Zoo. This groundbreaking achievement was conceived as a new strategy to help restore genetic diversity to the Przewalski’s horse species.
Cloning For Conservation: Now a portion of this lost genetic diversity may be recovered by cloning historic Przewalski’s horse from frozen cells. Successful breeding can increase genetic diversity by reintroducing lost variants to the surviving population. This is the hope for the new foal, Kurt, who was cloned from cells that had been cryopreserved at the SDZG Frozen Zoo in 1980. These were cells from a stallion that was born in 1975 in the UK, was transferred to the US in 1978, and lived until 1998. He was recorded as Stud Book number 615 (SB615) and known as “Kuporovic” by his zookeepers. Learn more about this cloning process.
The SB615 cell line was chosen for genetic rescue cloning because an analysis of the captive breeding pedigree revealed that the genome offers substantially more genetic variation than any living Przewalski’s horse. Now that the genetic variation from Kuporovic “lives” again in Kurt, Kurt may become the most important horse in the North American captive breeding population. He may also become the first cloned animal to restore lost genetic variation to its species.
“A Single Gene Causes Thelytokous Parthenogenesis, the Defining Feature of the Cape Honeybee Apis Mellifera Capensis”, Yagound et al 2020
2020-yagound.pdf: “A Single Gene Causes Thelytokous Parthenogenesis, the Defining Feature of the Cape Honeybee Apis mellifera capensis”, (2020-05-07; similar):
In honeybees, the ability of workers to produce daughters asexually, ie., thelytokous parthenogenesis, is restricted to a single subspecies inhabiting the Cape region of South Africa, Apis mellifera capensis. Thelytoky has unleashed new selective pressures and the evolution of traits such as social parasitism, invasiveness, and social cancer. Thelytoky arises from an abnormal meiosis that results in the fusion of two maternal pronuclei, restoring diploidy in newly laid eggs. The genetic basis underlying thelytoky is disputed. To resolve this controversy, we generated a backcross between thelytokous A. m. capensis and non-thelytokous A. m. scutellata from the neighboring population and looked for evidence of genetic markers that co-segregated with thelytokous reproduction in 49 backcross females. We found that markers associated with the gene GB45239 on chromosome 11, including non-synonymous variants, showed consistent co-segregation with thelytoky, whereas no other region did so. Alleles associated with thelytoky were present in all A. m. capensis genomes examined but were absent from all other honeybees worldwide including A. m. scutellata. GB45239 is derived in A. m. capensis and has a putative role in chromosome segregation. It is expressed in ovaries and is downregulated in thelytokous bees, likely because of polymorphisms in the promoter region. Our study reveals how mutations affecting the sequence and/or expression of a single gene can change the reproductive mode of a population.
[Keywords: thelytoky, honeybee, meiosis, reproductive mode]
“CC, world’s first cloned cat, turns 18 years old”, (2020-01-02; ; ; similar):
The first of her kind, CC the cloned cat is breaking more boundaries as she turns 18 years old. There are no big plans locally to mark the day, but CC—Carbon Copy or Copy Cat—will be the focus of a Dutch cartoon set for release today to celebrate her birthday, researcher and owner Duane Kraemer said.
…CC is not only enjoying life as the Kraemers’ pet, but she has her own condo called the “kitty house” behind the Kraemers’ house where she lives with her three offspring, sired by a cat named Smokey. Those offspring, just by existing, helped CC make headlines in the scientific community. There had not been much research done in the reproduction success of clones—and none had been done with a cat. Tim, Zip and Tess were born Sept. 1, 2006, along with a fourth kitten that was stillborn. Not knowing CC’s reaction would be to her kittens, Kraemer said, they found CC was “the perfect mother” and had the innate maternal instincts they were hoping she would exhibit. Besides proving clones can successfully reproduce, CC also proved not all clones die young. “Dolly the sheep, that was the first of the mammals to be cloned by nuclear transfer, had died at, I think, at 6 years of age”, Kraemer said. “So the fact that CC didn’t die young was news.” About 20% of cloned animals have developmental abnormalities of some kind, he said, with some being serious enough to result in the animal’s death at a young age or at birth. However, the other 80% born without those conditions “would probably live to a normal variation of ages.”
“The transcriptional legacy of developmental stochasticity”, (2019-12-12; similar):
Genetic variation, epigenetic regulation and major environmental stimuli are key contributors to phenotypic variation, but the influence of minor perturbations or “noise” has been difficult to assess in mammals. In this work, we uncover one major axis of random variation with a large and permanent influence: developmental stochasticity. By assaying the transcriptome of wild monozygotic quadruplets of the nine-banded armadillo, we find that persistent changes occur early in development, and these give rise to clear transcriptional signatures which uniquely characterize individuals relative to siblings. Comparing these results to human twins, we find the transcriptional signatures which define individuals exhibit conserved co-expression, suggesting a substantial fraction of phenotypic and disease discordance within mammals arises from developmental stochasticity.
One sentence summary
Longitudinal gene expression in identical armadillo quadruplets reveals a major role for developmental stochasticity.
2019-05-06-theexpresstribune-80percentofsouthkoreassnifferdogsarecloned.html: “Amid animal cruelty debate, 80% of South Korea’s sniffer dogs are cloned”, (2019-05-06; ; ; similar):
Some 80% of active sniffer dogs deployed by South Korea’s quarantine agency are cloned, data showed Monday, as activists express their concerns over potential animal abuse. According to the Animal and Plant Quarantine Agency, 42 of its 51 sniffer dogs were cloned from parent animals as of April, indicating such cloned detection dogs are already making substantial contributions to the country’s quarantine activities. The number of cloned dogs first outpaced their naturally born counterparts in 2014, the agency said. Of the active cloned dogs, 39 are currently deployed at Incheon International Airport, the country’s main gateway.
Deploying cloned dogs can save time and money over training naturally born puppies as they maintain the outstanding traits of their parents, whose capabilities have already been verified in the field, according to experts. While the average cost of raising one detection dog is over 100 million won (US$85,600), it is less than half that when utilising cloned puppies, they said.
Clone: “Dog Cloning For Special Forces: Breed All You Can Breed”, (2018-09-18; ; ; similar):
Decision analysis of whether cloning the most elite Special Forces dogs is a profitable improvement over standard selection procedures. Unless training is extremely cheap or heritability is extremely low, dog cloning is hypothetically profitable.
Cloning is widely used in animal & plant breeding despite steep costs due to its advantages; more unusual recent applications include creating entire polo horse teams and reported trials of cloning in elite police/Special Forces war dogs. Given the cost of dog cloning, however, can this ever make more sense than standard screening methods for selecting from working dog breeds, or would the increase in successful dog training be too low under all reasonable models to turn a profit?
I model the question as one of expected cost per dog with the trait of successfully passing training, success in training being a dichotomous liability threshold with a polygenic genetic architecture; given the extreme level of selection possible in selecting the best among already-elite Special Forces dogs and a range of heritabilities, this predicts clones’ success probabilities. To approximate the relevant parameters, I look at some reported training costs and success rates for regular dog candidates, broad dog heritabilities, and the few current dog cloning case studies reported in the media.
Since none of the relevant parameters are known with confidence, I run the cost-benefit equation for many hypothetical scenarios, and find that in a large fraction of them covering most plausible values, dog cloning would improve training yields enough to be profitable (in addition to its other advantages).
As further illustration of the use-case of screening for an extreme outcome based on a partial predictor, I consider the question of whether height PGSes could be used to screen the US population for people of NBA height, which turns out to be reasonably doable with current & future PGSes.
- Modeling the SF selection problem
- Base Rates
- Liability threshold model
- See Also
“In Vitro Gametogenesis and Reproductive Cloning: Can We Allow One While Banning the Other?”, Segers et al 2018
2018-segers.pdf: “In vitro gametogenesis and reproductive cloning: Can we allow one while banning the other?”, Seppe Segers, Guido Pennings, Wybo Dondorp, Guido de Wert, Heidi Mertes (2018-01-01; )
Dog cloning as a concept is no longer infeasible. Starting with Snuppy, the first cloned dog in the world, somatic cell nuclear transfer (SCNT) has been continuously developed and used for diverse purposes. In this article we summarise the current method for SCNT, the normality of cloned dogs and the application of dog cloning not only for personal reasons, but also for public purposes.
Animal cloning has gained popularity as a method to produce genetically identical animals or superior animals for research or industrial uses. However, the long-standing question of whether a cloned animal undergoes an accelerated aging process is yet to be answered. As a step towards answering this question, we compared longevity and health of Snuppy, the world’s first cloned dog, and its somatic cell donor, Tai, a male Afghan hound. Briefly, both Snuppy and Tai were generally healthy until both developed cancer to which they succumbed at the ages of 10 and 12 years, respectively. The longevity of both the donor and the cloned dog was close to the median lifespan of Afghan hounds which is reported to be 11.9 years. Here, we report creation of 4 clones using adipose-derived mesenchymal stem cells from Snuppy as donor cells. Clinical and molecular follow-up of these reclones over their lives will provide us with an unique opportunity to study the health and longevity of cloned animals compared with their cell donors.
2016-oh.pdf: “Propagation of elite rescue dogs by somatic cell nuclear transfer”, Hyun Ju Oh, Jin Choi, Min Jung Kim, Geon A. Kim, Young Kwang Jo, Yoo Bin Choi, Byeong Chun Lee (2016-01-01; )
2015-gianola.pdf: “One Hundred Years of Statistical Developments in Animal Breeding”, (2014-11-03; ; ; similar):
Statistical methodology has played a key role in scientific animal breeding. ~1hundred 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.
2014-choi.pdf: “Behavioral Analysis of Cloned Puppies Derived from an Elite Drug-Detection Dog”, (2014-01-01; )
“Whole genome comparison of donor and cloned dogs”, (2013-10-21):
Cloning is a process that produces genetically identical organisms. However, the genomic degree of genetic resemblance in clones needs to be determined.
In this report, the genomes of a cloned dog and its donor were compared.
Compared with a human monozygotic twin, the genome of the cloned dog showed little difference from the genome of the nuclear donor dog in terms of single nucleotide variations, chromosomal instability and telomere lengths. These findings suggest that cloning by somatic cell nuclear transfer produced an almost identical genome.
The whole genome sequence data of donor and cloned dogs can provide a resource for further investigations on epigenetic contributions in phenotypic differences.
Profile of the development & launch of the SweeTango apple, a successor to Honeycrisp (via a hybridization with Zestar), developed by the University of Minnesota apple breeding program, which has been running since 1878 and created 27 notable apples (earning its role as the state fruit).
Breeding programs like that are part of why Americans have historically shifted from consuming hard cider (made with inedible wild-types) to ‘eating apples’, but progress was set back by a drastic decrease in variety to the McIntosh/Golden Delicious/Red Delicious triumvirate—Red Delicious degrading rapidly in quality. The apple revolution began in the 1970s when Granny Smith proved US consumers would buy a better apple, and was followed by the Fuji, Braeburn, and Gala.
How does one breed a new apple? Apples do not breed true and every offspring is wildly different. Apple breeders use brute force and brutally stringent screening: an acre of thousands of saplings will be grown, and in all, the breeders will walk the row, grab 1 apple, chew it briefly, spit it out, and mark the tree if good. Any sapling which is marked several years in a row (a few score out of thousands) survives; clones of it will be transplanted elsewhere for further testing, and evaluated similarly for another decade. If and only a new apple tree & clones pass all these tests, will it even be considered for commercialization.
“I’d like to give a tree a couple chances, but I just don’t have the mouth time for that”, Bedford explained. “So it’s one strike and you’re out. With all these new trees coming on each year, you won’t have space unless you thin out the duds.” He sprayed another tree trunk with the mark of death. “But it is kind of nerve-racking, because you want to give the tree a chance to do its best. No one wants to be known as the guy who killed the next Honeycrisp.”
The winner of such a process must be both brilliant and lucky, and Honeycrisp was both. But UMinn breeders watched with dismay as they felt the released Honeycrisp saplings were mistreated or poorly-raised by careless commercial growers, and decided the next apple, SweeTango, would be a “club apple”: it would be fully patented & controlled, and sold only to select apple growers who would be required to follow stringent rules.
The “club apple” business model has proven to be its own revolution by internalizing the costs & benefits, incentivizing the creation of a dizzying variety of new apples reaching the American grocery market every year.
He rolled the dice again. This time, he was mimicking what he and his colleagues have been doing quietly around the globe for more than a half-century—using radiation to scramble the genetic material in crops, a process that has produced valuable mutants like red grapefruit, disease-resistant cocoa and premium barley for Scotch whiskey…The process leaves no residual radiation or other obvious marks of human intervention. It simply creates offspring that exhibit new characteristics.
Though poorly known, radiation breeding has produced thousands of useful mutants and a sizable fraction of the world’s crops, Dr. Lagoda said, including varieties of rice, wheat, barley, pears, peas, cotton, peppermint, sunflowers, peanuts, grapefruit, sesame, bananas, cassava and sorghum. The mutant wheat is used for bread and pasta and the mutant barley for beer and fine whiskey.
The mutations can improve yield, quality, taste, size and resistance to disease and can help plants adapt to diverse climates and conditions…“Spontaneous mutations are the motor of evolution”, Dr. Lagoda said. “We are mimicking nature in this. We’re concentrating time and space for the breeder so he can do the job in his lifetime. We concentrate how often mutants appear—going through 10,000 to one million—to select just the right one.”
Radiation breeding is widely used in the developing world, thanks largely to the atomic agency’s efforts. Beneficiaries have included Bangladesh, Brazil, China, Costa Rica, Egypt, Ghana, India, Indonesia, Japan, Kenya, Nigeria, Pakistan, Peru, Sri Lanka, Sudan, Thailand and Vietnam.
…Plant scientists say radiation breeding could play an important role in the future. By promoting crop flexibility, it could help feed billions of added mouths despite shrinking land and water, rising oil and fertilizer costs, increasing soil exhaustion, growing resistance of insects to pesticides and looming climate change. Globally, food prices are already rising fast.
“It’s not going to solve the world food crisis”, said J. Neil Rutger, former director of the Dale Bumpers National Rice Research Center in Stuttgart, Ark. “But it will help. Modern plant breeders are using every tool they can get.”
The method was discovered some 80 years ago when Lewis J. Stadler of the University of Missouri used X-rays to zap barley seeds. The resulting plants were white, yellow, pale yellow and some had white stripes—nothing of any practical value.
But the potential was clear. Soon, by exposing large numbers of seeds and young plants, scientists produced many more mutations and found a few hidden beneficial ones. Peanuts got tougher hulls. Barley, oats and wheat got better yields. Black currants grew.
…In the 1950s and 1960s, the United States government promoted the method as part of its “atoms for peace” program and had notable successes. In 1960, disease heavily damaged the bean crop in Michigan—except for a promising new variety that had been made by radiation breeding. It and its offspring quickly replaced the old bean.
In the early 1970s, Dr. Rutger, then in Davis, Calif., fired gamma rays at rice. He and his colleagues found a semi-dwarf mutant that gave much higher yields, partly because it produced more grain. Its short size also meant it fell over less often, reducing spoilage. Known as Calrose 76, it was released publicly in 1976.
Today, Dr. Rutger said, about half the rice grown in California derives from this dwarf. Now retired in Woodland, Calif., he lives just a few miles from where the descendants grow, he said.
A similar story unfolded in Texas. In 1929, farmers stumbled on the Ruby Red grapefruit, a natural mutant. Its flesh eventually faded to pink, however, and scientists fired radiation to produce mutants of deeper color—Star Ruby, released in 1971, and Rio Red, released in 1985. The mutant offspring now account for about 75% of all grapefruit grown in Texas.
Though the innovations began in the United States, the method is now used mostly overseas, with Asia and Europe the leading regions. Experts cited 2 main reasons: domestic plant researchers over the decades have already made many, perhaps most of the easiest improvements that can be achieved with radiation, and they now focus on highly popular fields like gene splicing.
“Most scientists here would say it’s pretty primitive”, Norman T. Uphoff, a professor of government and international agriculture at Cornell University, said of the method. “It’s like being in a huge room with a flashlight.” But the flashlight is cheap, which has aided its international spread.
…Dr. Lagoda said a rust fungus threatened the Japanese pear, a pear with the crisp texture characteristic of apples. But one irradiated tree had a branch that showed resistance. He said the Japanese cloned it, successfully started a new crop and with the financial rewards “paid for 30 years of research.”
The payoff was even bigger in Europe, where scientists fired gamma rays at barley to produce Golden Promise, a mutant variety with high yields and improved malting. After its debut in 1967, brewers in Ireland and Britain made it into premium beer and whiskey. It still finds wide use. “The secret”, reads a recent advertisement for a single malt Scotch whiskey costing $69.74$49.992007 a bottle, is “the continued use of finest Golden Promise barley and the insistence on oak sherry casks from Spain.”
…Starting roughly a decade ago, for instance, the atomic agency helped scientists fight a virus that was killing cocoa trees in Ghana, which produces about 15% of the world’s chocolate. The virus was killing and crippling millions of trees. In the city of Accra on the Atlantic coast, at the laboratories of the Ghana Atomic Energy Commission, the scientists exposed cocoa plant buds to gamma rays. The mutants included one that endowed its offspring with better resistance to the killer virus.
…The atomic agency had similar success in the Peruvian Andes, where some 3 million people live on subsistence farming. The region, nearly 2 miles high, has extremely harsh weather. But 9 new varieties of barley improved harvests to the point that farmers had surplus crops to sell.
In 2006, Prof. Gomes Pando won the Peruvian prize for Good Government Practices for her work on the radiation mutants.
In Vietnam, the agency has worked closely with local scientists to improve production of rice, a crop that accounts for nearly 70% of the public’s food energy.
One mutant had yields up to 3× higher than its parent and grew well in acidic and saline soils, allowing farmers to use it in coastal regions, including the Mekong Delta.
Last year, a team of 10 Vietnamese scientists wrote in an agency journal, Plant Mutation Reports, that the nation had sown the new varieties across more than one million hectares, or 3,860 square miles. The new varieties, they added, “have already produced remarkable economic and social impacts, contributing to poverty alleviation in some provinces.”
“Traits and Genotypes May Predict the Successful Training of Drug Detection Dogs”, Maejima et al 2007
2007-maejima.pdf: “Traits and genotypes may predict the successful training of drug detection dogs”, (2007; ; ; similar):
In Japan, ~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).
II. When the Smoke Clears
The mind, that rambling bear, ransacks the sky
In search of honey,
Fish, berries, carrion. It minds no laws…
As if the heavens were some canvas tent,
It slashes through the firmament
To prise up the sealed stores with its big paws.
The mind, that sovereign camel, sees the sky
For what it is:
Each star a grain of sand along the vast
Passage to that oasis where, below
The pillared palms, the portico
Of fronds, the soul may drink its fill at last.
The mind, that gorgeous spider, webs the sky
With lines so sheer
They all but vanish, and yet star to star
(Thread by considered thread) slowly entwines
The universe in its designs—
Un-earthing patterns where no patterns are.
The mind, that termite, seems to shun the sky.
It burrows down,
Tunneling in upon that moment when,
In Time—its element—will come a day
The longest-shadowed tower sway,
Unbroken sunlight fall to earth again.
…DNA was unspooled in the year
I was born, and the test-tube births
Of cloned mammals emerged in a mere
Half-century; it seems the earth’s
Future’s now in the hands of a few
Techies on a caffeinated all-nighter who
Sift the gene-alphabet like Scrabble tiles
And our computer geeks are revealed, at last,
As those quick-handed, sidelined little mammals
In the dinosaurs’ long shadows—those least-
Likely-to-succeed successors whose kingdom come
Was the globe itself (an image best written down,
Perhaps, beneath a streetlamp, late, in some
Star-riddled Midwestern town).
He wrote boys’ books and intuitively
Recognized that the real
Realist isn’t the one who details
Lowdown heartland factories and farms
As if they would last, but the one who affirms,
From the other end of the galaxy,
Ours is the age of perilous miracles.
Somatic cell nuclei of giant pandas can dedifferentiate in enucleated rabbit ooplasm, and the reconstructed eggs can develop to blastocysts.
In order to observe whether these interspecies cloned embryos can implant in the uterus of an animal other than the panda, we transferred approximately 2,300 panda-rabbit cloned embryos into 100 synchronized rabbit recipients, and none became pregnant. In another approach, we co-transferred both panda-rabbit and cat-rabbit interspecies cloned embryos into the oviducts of 21 cat recipients. 14 recipients exhibited estrus within 35 days; 5 recipients exhibited estrus 43–48 days after embryo transfer; and the other 2 recipients died of pneumonia, one of which was found to be pregnant with 6 early fetuses when an autopsy was performed.
Microsatellite DNA analysis of these early fetuses confirmed that 2 were from giant panda-rabbit cloned embryos. The results demonstrated that panda-rabbit cloned embryos can implant in the uterus of a third species, the domestic cat. By using mitochondrial-specific probes of panda and rabbit, we found that mitochondria from both panda somatic cells and rabbit ooplasm coexisted in early blastocysts, but mitochondria from rabbit ooplasm decreased, and those from panda donor cells dominated in early fetuses after implantation.
Our results reveal that mitochondria from donor cells may substitute those from recipient oocytes in post-implanted, interspecies cloned embryos.
The first topic, which consists of the bulk of this chapter, is using index selection to improve a single trait. One can have a number of measures of the same trait in either relatives of a focal individual or as multiple measures of the same trait in a single individual, or both. How does one best use this information? We start by developing the general theory for using an index to improve the response in a single trait (which follows as a simplification of the Smith-Hazel index). We then apply these results to several important cases—a general analysis when either phenotypic or genotypic correlations are zero, improving response using repeated measurements of a characters over time, and using information from relatives to improve response with a special focus on combined selection (the optimal weighting of individual and family information, proving many of the details first presented in Chapter 17). As we will see in Chapter 35, the mixed-model power of BLUP provides a better solution to many of these problems, but index selection is both historically important as well as providing clean analytic results. In contrast to the first topic, the final three are essentially independent of each other and we try to present them as such (so that the reader can simply turn to the section of interest without regard to previous material in this chapter). They include selection on a ratio, selection on sex-specific and sexually-dimorphic traits, and finally selection on the environmental variance σ2E when it shows heritable variation (expanding upon results from Chapter 13).
While Chapters 28 and 29 present the basic theory for multivariate response, how, in practice, does one perform artificial selection on multiple traits? One of the commonest schemes is to construct some sort of index, wherein the investigator assigns (either explicitly or implicitly) a weighting scheme to each trait, creating an univariate character that becomes the target of selection. For example, if z is the vector of character values measured in an individual, the most common index is a linear combination Pbizi = bT z and most of our discussion focuses on such linear indices. We start with a general review of the theory of selection on a linear index and then cover in great detail the Smith-Hazel index (the index giving the largest expected response in a specified linear combination of characters) and its extensions. We also discuss a number of other indices for different purposes, such as restricted (constraining changes in specified traits) and desired-gains (specifying how the components, rather than the index, will evolve) indices. We conclude our discussion of index selection by considering how to best handle nonlinear indices. We finish the chapter by examining the other approach for selecting on multiple traits, namely choosing traits sequentially. Tandem selection, focusing on a single trait each generation (where the focal trait changes over generations) is one such approach, while the other is to select different traits at different times within the life span of single individuals (independent culling and multistage index selection).