Keywords: Rodents
Genetically modified mice could fight Lyme disease in Massachusetts
35429Dave Puglisi, 7News, 2026-01-29 10:43:05.
Tiny insects are spreading a devastating disease. Scientists at Massachusetts Institute of Technology (MIT) believe they’ve discovered something that could help stop Lyme disease before it starts. “The right side of my body went numb. I felt disoriented. My heart was racing,” said Brandi Dean. Dean thought what she was experiencing was a stroke but it was actually the start of a 10-year battle with Lyme disease. “It’s a devastating illness, emotionally, physically, and financially,” she said. The illness began with a tick bite that spread bacteria throughout her body. “I was really struggling to just survive every day and to take care of my kids,” said Dean. Brandi pushed through muscle pain, dizziness and exhaustion so severe she couldn’t walk down the stairs. “I would literally scoot down each stair. I had very little energy to walk,” said Dean. “It was frightening at that time.” Doctor Sam Telford, a professor of infectious disease and global health at Tufts University, has studied ticks for more than 40-years. He says mice are a perfect host for several diseases ticks can spread. “They’re very good hosts for the bacteria. They suffer no disease from having the bacteria,” said Telford. “They pass it back-and-forth and us humans are collateral damage.”
Genetically engineered mice could take the bite out of Lyme disease on Nantucket, scientists say
35149Jon LaPook, Denise Schrier Cetta, Aliza Chasan, Katie Brennan, CBS News, 2025-09-21 10:07:27.
Over the past 40 years, Dr. Timothy Lepore has been the emergency room head, sole surgeon and medical examiner on Nantucket, a small island off Cape Cod, Massachusetts. Today he runs the only private practice, where he treats dozens of patients with Lyme disease each year. About 15% of residents on the island have been afflicted with the disease, which can cause a wide range of symptoms like a fever, rash, facial paralysis, an irregular heartbeat and arthritis. Lepore, 80, may finally be able to retire if a team of scientists' dream to curb the transmission of Lyme disease on the island becomes a reality. The scientists' target is not the deer or ticks often associated with the disease: it's wild mice, the main host of Lyme bacteria. The hope is that by genetically engineering mice to be immune to Lyme and releasing them in Nantucket, the population of mice able to spread Lyme disease on the island will shrink. The problem on Nantucket can be traced back to 1926, when the community voted to import two female deer to the island to give a lone buck company. On top of that, by the 1950s, half the land on the island was put into conservation. The untamed brush and wild grasslands create an ideal ecosystem for Lyme's hosts to thrive. As the deer population grew, so did the population of ticks. Deer don't get Lyme, but female ticks feed on them, and then lay as many as 2,000 eggs in a single batch. Deer also spread the disease as thousands of them carry ticks across Nantucket. Not all ticks carry Lyme disease, and a tick bite doesn't guarantee the transmission. Even if the tick is carrying Lyme, the tick has to be attached for more than 24 hours to infect someone.
Maximising Eradication Potential of Rat Gene Drives Using a Two-Target Homing Rescue Strategy: Spatial Modelling of Empirical Data
34817Birand, A., Gierus, L., Prowse, T., Cassey, P., Thomas, P.Q., Molecular Ecology, 2025-05-04 16:12:38.
Gene drives are genetic elements with positively biased transmission and may be useful tools to suppress mammalian pests that threaten biodiversity worldwide. While gene drives are progressing in mice, less is known about their potential for invasive rat control. A recent report has provided the first data on germline gene conversion in rats, demonstrating that modest homing rates (up to 67%) can be achieved in females. Here, we apply these empirically derived values to investigate the potential of various gene drive strategies to suppress an island population of 200,000 rats, using our stochastic, spatially explicit, individual-based modelling framework. Standard homing drives embedded in haplosufficient fertility or viability genes failed to eradicate, but achieved permanent population suppression. In contrast, a two-target design with a homing rescue (HR) drive embedded in a haplolethal gene that also targets an independent fertility or viability gene demonstrated considerable suppression potential. Remarkably, an HR drive targeting a haplosufficient female fertility gene showed robust eradication even at the relatively low homing rates previously demonstrated in rats. Interestingly, homing rate had a relatively low influence on eradication probability while cutting efficiency at the haplolethal gene was critical. Further, as long as the latter was similar to the cutting and subsequent knockout of the unlinked female fertility gene, then eradication could be achieved across a range of homing rates. Together, these results suggest that modest homing rates, such as have been demonstrated in rats and other species, can potentially be leveraged for population suppression, offering new opportunities for gene drive development.
Reenacting a mouse genetic evolutionary arms race in yeast reveals that SLXL1/SLX compete with SLY1/2 for binding to Spindlins
34550M.F. Arlt,A.N. Kruger,C.M. Swanepoel,& J.L. Mueller, Proceedings of the National Academy of Sciences, 122. 2025-03-04 10:54:14.
In the house mouse, an evolutionary arms race between proteins encoded by the X-linked Slxl1/Slx and Y-linked Sly gene families during spermatogenesis can distort offspring sex ratio, but how these proteins compete remains unknown. We report how SLXL1/SLX competes with SLY1/SLY2 by demonstrating their dose-dependent competitive binding to Spindlins, the key protein domains and rapidly evolving residues and exons that drive the competition, and how the competition is likely between complex multimers. Our findings have broad implications for the mechanics of evolutionary arms and how competition between sex chromosomes influences X- versus Y-sperm fitness and sex ratio.
What are the evolutionary considerations of rodent gene drives for conservation and human health?
34662Triangle Center for Evolutionary Medicine, YouTube, 2025-02-21 09:38:19.
Biodiversity, human health, and food security can all be impacted by invasive rodents. These negative impacts are particularly seen on islands, where rodent eradications with traditional methods can sometimes fail due to evolutionary resistance. Gene drives may offer an approach to the challenge of rodent eradication on islands. My primary research focus is wild house mice (Mus musculus) and the potential use of gene drive technology. Mus are a key genetic model system and an invasive species on many islands worldwide. Evolutionarily sound approaches are needed, and we are investigating ways to tailor genetic techniques to unique island populations. Using models on gene drive mice can help us predict how laboratory/wild mice would introgress into a population. Evolutionary resistance is also possible; the mice may evade our best methods. However, gene drive technology in rodents can potentially produce significant gains for conservation and society. To this end, a broad interdisciplinary lens with many differing perspectives is required.
Meiotic Drive and Speciation
34057Jeremy B. Searle and Fernando Pardo-Manuel de Villena, Annual Review of Genetics, 58:341-363. 2024-12-16 15:22:27.
Meiotic drive is the biased transmission of alleles from heterozygotes, contrary to Mendel's laws, and reflects intragenomic conflict rather than organism-level Darwinian selection. Theory has been developed as to how centromeric properties can promote female meiotic drive and how conflict between the X and Y chromosomes in males can promote male meiotic drive. There are empirical data that fit both the centromere drive and sex chromosome drive models. Sex chromosome drive may have relevance to speciation through the buildup of Dobzhansky-Muller incompatibilities involving drive and suppressor systems, studied particularly in Drosophila. Centromere drive may promote fixation of chromosomal rearrangements involving the centromere, and those fixed rearrangements may contribute to reproductive isolation, studied particularly in the house mouse. Genome-wide tests suggest that meiotic drive promotes allele fixation with regularity, and those studying the genomics of speciation need to be aware of the potential impact of such fixations on reproductive isolation. New species can originate in many different ways (including multiple factors acting together), and a substantial body of work on meiotic drive point to it being one of the processes involved.
How genetically engineered mice could stop the spread of Lyme disease
33874Cristela Guerra and Stephanie Brown, WBUR Radio Boston, 2024-12-10 16:36:59.
New England has some of the highest rates of Lyme disease in the country. MIT researchers are trying to fight the disease in a project that involves releasing hundreds of thousands of engineered mice onto the shores of Nantucket and Martha's Vineyard. On Radio Boston, Kevin Esvelt, an associate professor at the MIT Media Lab and the inventor of CRISPR-based gene drive, discusses the project.
The Meiotic Drive: Intragenomic Competition and Selection
33610I. A. Zakharov, Russian Journal of Genetics, 60:1311-1318. 2024-11-12 12:02:24.
The article considers the distribution and mechanisms of the meiotic drive as a phenomenon manifested in unequal transmission of gene alleles and/or homologous chromosomes into gametes during meiosis. The meiotic drive has been studied in the most detail in Drosophila, mice, corn, and ascomycete fungi of the genera Neurospora and Podospora. The consequence of the meiotic drive is a shift in the frequencies of alleles in the gene pool and the maintenance of nonadaptive traits in the population.
Viral gene drive spread during herpes simplex virus 1 infection in mice
31625Walter, M., Haick, A.K., Riley, R. et al., Nature Communications, 15. 2024-09-17 21:18:39.
Gene drives are genetic modifications designed to propagate efficiently through a population. Most applications rely on homologous recombination during sexual reproduction in diploid organisms such as insects, but we recently developed a gene drive in herpesviruses that relies on co-infection of cells by wild-type and engineered viruses. Here, we report on a viral gene drive against human herpes simplex virus 1 (HSV-1) and show that it propagates efficiently in cell culture and during HSV-1 infection in mice. We describe high levels of co-infection and gene drive-mediated recombination in neuronal tissues during herpes encephalitis as the infection progresses from the site of inoculation to the peripheral and central nervous systems. In addition, we show evidence that a superinfecting gene drive virus could recombine with wild-type viruses during latent infection. These findings indicate that HSV-1 achieves high rates of co-infection and recombination during viral infection, a phenomenon that is currently underappreciated. Overall, this study shows that a viral gene drive could spread in vivo during HSV-1 infection, paving the way toward therapeutic applications.
An egg-sabotaging mechanism drives non-Mendelian transmission in mice
31028Frances E. Clark, Naomi L. Greenberg, Duilio M.Z.A. Silva, et al, Current Biology, 2024-08-05 11:40:23.
Selfish genetic elements drive in meiosis to distort their transmission ratio and increase their representation in gametes, violating Mendel’s law of segregation. The two established paradigms for meiotic drive, gamete killing and biased segregation, are fundamentally different. In gamete killing, typically observed with male meiosis, selfish elements sabotage gametes that do not contain them. By contrast, killing is predetermined in female meiosis, and selfish elements bias their segregation to the single surviving gamete (i.e., the egg in animal meiosis). Here, we show that a selfish element on mouse chromosome 2, Responder to drive 2 (R2d2), drives using a hybrid mechanism in female meiosis, incorporating elements of both killing and biased segregation. We propose that if R2d2 is destined for the polar body, it manipulates segregation to sabotage the egg by causing aneuploidy, which is subsequently lethal in the embryo, ensuring that surviving progeny preferentially contain R2d2. In heterozygous females, R2d2 orients randomly on the metaphase spindle but lags during anaphase and preferentially remains in the egg, regardless of its initial orientation. Thus, the egg genotype is either euploid with R2d2 or aneuploid with both homologs of chromosome 2, with only the former generating viable embryos. Consistent with this model, R2d2 heterozygous females produce eggs with increased aneuploidy for chromosome 2, increased embryonic lethality, and increased transmission of R2d2. In contrast to typical gamete killing of sisters produced as daughter cells in a single meiosis, R2d2 prevents production of any viable gametes from meiotic divisions in which it should have been excluded from the egg.
Research breakthrough in genetic biocontrol striving to transform pest management: Centre for Invasive Species Solutions
28332ARR News, Australian Rural and Regional News, 2023-11-02 13:31:54.
A potential new non-lethal and ethical approach to control invasive mammal pests was showcased at a briefing held at the South Australian Health and Medical Research Institute in Adelaide on Tuesday 31 October. Hosted by the Centre for Invasive Species Solutions and the University of Adelaide, the briefing introduced guests to a world-first breakthrough in gene drive technology. The University of Adelaide discovery is the first time a new genetic tool has been identified that is able to induce female infertility into a mouse population, offering a non-lethal way to control mice and rats. Importantly, these findings could be transferred to control other pests, such as rabbits and feral cats.
Meiotic drive of noncentromeric loci in mammalian meiosis II eggs
26477D. M. Silva and T. Akera, Curr Opin Genet Dev, 81:102082. 2023-07-03 08:21:48.
The germline produces haploid gametes through a specialized cell division called meiosis. In general, homologous chromosomes from each parent segregate randomly to the daughter cells during meiosis, providing parental alleles with an equal chance of transmission. Meiotic drivers are selfish elements who cheat this process to increase their transmission rate. In female meiosis, selfish centromeres and noncentromeric drivers cheat by preferentially segregating to the egg cell. Selfish centromeres cheat in meiosis I (MI), while noncentromeric drivers can cheat in both meiosis I and meiosis II (MII). Here, we highlight recent advances on our understanding of the molecular mechanisms underlying these genetic cheating strategies, especially focusing on mammalian systems, and discuss new models of how noncentromeric selfish drivers can cheat in MII eggs.
Probing “Selfish” Centromeres Unveils an Evolutionary Arms Race
24935M. Lampson, The Scientist, 2023-04-03 10:08:47.
The so-called Robertsonian (Rb) fusions that led to these rapid karyotype changes are relatively common chromosomal rearrangements. But their accumulation in the populations of Madeira Island and in multiple other isolated mouse populations elsewhere is likely due to another influencing factor: the preferential segregation of the Rb fusion into the egg rather than into the discarded polar bodies that form during female meiosis. We usually think of the chromosome segregation machinery as ensuring unbiased, random segregation. As we learn in high school biology, if a diploid individual carries two different alleles of a gene (i.e., is heterozygous), then either allele is equally likely to end up in a haploid gamete. This law explains the 3:1 ratio of phenotypes that Mendel observed in his classic studies of heredity. Scientists have known for decades, however, that selfish genes can subvert Mendelian segregation to increase their frequency in the next generation, a phenomenon known as meiotic drive. The Madeira mice suggest that fusion chromosomes can also drive unequal inheritance.
Gene drive-mediated population elimination for biodiversity conservation. When you come to a fork in the road, take it
24281B. A. Hay and M. Guo, Proceedings of the National Academy of Sciences, 119:e2218020119. 2022-12-20 14:19:44.
How can the ability of t w2 to spread at super-Mendelian frequencies be utilized even if it is unable to directly drive the population to an unfit state? Gierus, Birand, and colleagues proposed placing Cas9 and a gRNA at a neutral position within the t haplotype. In this hybrid gene drive element, which they refer to as tCRISPR, Cas9 and the gRNA cleave and (hopefully) create loss-of-function (LOF) alleles in the male germ line of the prolactin (Prl) gene, which is required for female fertility. The goal with tCRISPR is for t-based segregation distortion in males to pump the Cas9/gRNAs cassette to high frequency within the population. The latter, through cleavage followed by inaccurate repair in males, will continuously produce LOF alleles at the independently segregating Prl locus. The hope is that the combination of t-based drive and accumulation of Prl LOF alleles will drive the population to an unfit state that contains a high frequency of infertile homozygous Prl mutant females along with some frequency of infertile homozygous t males. The combination of these two effects, they propose, could eliminate populations under a wider range of parameters than with t w2 alone
New CRISPR tech makes it possible to wipe out invasive mice
241812022-12-11 11:12:20.
A natural gene drive could steer invasive rodents on islands to extinction
24129B. Brookshire, ScienceNews, 2022-12-05 09:12:58.
In the battle against the invasive house mouse on islands, scientists are using the rodent’s own genes against it. With the right tweaks, introducing a few hundred genetically altered mice could drive an island’s invasive mouse population to extinction in about 25 years, researchers report in the Nov. 15 Proceedings of the National Academy of Sciences. The trick is adding the changes to a section of mouse DNA that gets inherited far more often than it should. Scientists have been creating similar extra-inheritable genes — called gene drives — in the lab. The chunks are designed to get passed on to most or all of an animal’s offspring instead of the usual half, and make those offspring infertile in the bargain. Scientists have used gene drives to reduce populations of mosquitoes and fruit flies (SN: 12/17/18). But mammals are a different story. Scientists have previously synthesized a gene drive that gets passed on in mice about 80 percent of the time (SN: 1/23/19). But the drive isn’t strong enough to stop a population quickly. Luckily, nature has it handled. A haplotype is a naturally occurring group of genes that gets passed on as a unit during replication. The genome of the house mouse (Mus musculus) has a particular haplotype, called the t haplotype, that gets passed on to offspring more than 95 percent of the time, instead of the typical 50 percent.
Gene drive could be used to wipe out invasive mice on islands
23862M. Le Page, NewScientist, 2022-11-11 10:11:35.
For the first time, researchers have created a gene drive – a kind of genetic parasite – that could be used to eradicate mammalian pests such as mice by making them infertile. The technology could provide a humane alternative to the poison baits currently used to tackle invasive mice on islands, which have severe impacts on native birds, reptiles and plants. “It’s the first example of a mammalian gene drive technology that has had proof of concept in a laboratory setting,” says Paul Thomas at the University of Adelaide in Australia. Most animals have two copies of each chromosome, but their offspring gets only one copy from each parent. This means that if a piece of DNA is added to one chromosome of an individual, only half its offspring will inherit it. Gene drives are bits of DNA that encode various mechanisms for cheating the system and ensuring they get inherited by more than half of offspring. This means they can spread in a population even if they are harmful. Various kinds of natural gene drives have been discovered. In 2013, Kevin Esvelt at Massachusetts Institute of Technology created the first synthetic gene drive using the gene-editing technology CRISPR. Such CRISPR-based gene drives work extremely well in insects and several teams hope to use them to prevent the spread of malaria, either by wiping out mosquitoes or by making them less likely to infect people.
World first trial to eradicate mice through gene modification
23838I. Mannix, COSMOS, 2022-11-10 09:51:29.
Mouse populations could be eradicated in some areas through new gene modification technology to render female mice infertile. The technology – called t-CRISPR – was previously developed to target malaria-transmitting mosquitoes. This is the first proof of concept for its use as a mammalian genetic biocontrol tool targeting house mice, which is an invasive pest in Australia. In time, it could be used to control rodents on islands and landmasses where they cause widespread destruction. The research, published in Proceedings of the National Academy of Sciences, is the first time t-CRISPR has been successfully tested on mammals in a laboratory setting, according to senior author Professor Paul Thomas. Computer modelling conducted by the team suggests about 250 gene-modified mice could eradicate an island population of 200,000 mice in around 20 years. “We have had mouse plagues in Australia for 150 years and existing controls, like baits, cause inhumane death and are expensive and labour intensive to deploy,” says Thomas, who works across the University of Adelaide and the South Australian Health and Medical Research Institute.
Gene drive technology to suppress invasive mice
23843University of Adelaide, Phys Org, 2022-11-09 09:55:57.
Researchers at the University of Adelaide have released their first findings on the potential effectiveness of revolutionary gene drive technology to control invasive mice. The team has developed a world-first proof of concept for the technology—called t-CRISPR—using laboratory mice. Using sophisticated computer modeling performed by co-first author Dr. Aysegul Birand, the researchers also found about 250 gene-modified mice could eradicate an island population of 200,000 mice in around 20 years. The results of the study have been published today in Proceedings of the National Academy of Sciences.
Leveraging a natural murine meiotic drive to suppress invasive populations
23835L. Gierus, A. Birand, M. D. Bunting, G. I. Godahewa, S. G. Piltz, K. P. Oh, A. J. Piaggio, D. W. Threadgill, J. Godwin, O. Edwards, P. Cassey, J. V. Ross, T. A. A. Prowse and P. Q. Thomas, Proceedings of the National Academy of Sciences, 119:e2213308119. 2022-11-08 09:36:13.
Invasive rodents are a major cause of environmental damage and biodiversity loss, particularly on islands. Unlike insects, genetic biocontrol strategies including population-suppressing gene drives with biased inheritance have not been developed in mice. Here, we demonstrate a gene drive strategy (t(CRISPR)) that leverages super-Mendelian transmission of the t haplotype to spread inactivating mutations in a haplosufficient female fertility gene (Prl). Using spatially explicit individual-based in silico modeling, we show that t(CRISPR) can eradicate island populations under a range of realistic field-based parameter values. We also engineer transgenic t(CRISPR) mice that, crucially, exhibit biased transmission of the modified t haplotype and Prl mutations at levels our modeling predicts would be sufficient for eradication. This is an example of a feasible gene drive system for invasive alien rodent population control.
Meiotic drive in house mice: mechanisms, consequences, and insights for human biology
23233U. P. Arora and B. L. Dumont, Chromosome Research, 2022-07-13 06:38:49.
Meiotic drive occurs when one allele at a heterozygous site cheats its way into a disproportionate share of functional gametes, violating Mendel's law of equal segregation. This genetic conflict typically imposes a fitness cost to individuals, often by disrupting the process of gametogenesis. The evolutionary impact of meiotic drive is substantial, and the phenomenon has been associated with infertility and reproductive isolation in a wide range of organisms. However, cases of meiotic drive in humans remain elusive, a finding that likely reflects the inherent challenges of detecting drive in our species rather than unique features of human genome biology. Here, we make the case that house mice (Mus musculus) present a powerful model system to investigate the mechanisms and consequences of meiotic drive and facilitate translational inferences about the scope and potential mechanisms of drive in humans. We first detail how different house mouse resources have been harnessed to identify cases of meiotic drive and the underlying mechanisms utilized to override Mendel's rules of inheritance. We then summarize the current state of knowledge of meiotic drive in the mouse genome. We profile known mechanisms leading to transmission bias at several established drive elements. We discuss how a detailed understanding of meiotic drive in mice can steer the search for drive elements in our own species. Lastly, we conclude with a prospective look into how new technologies and molecular tools can help resolve lingering mysteries about the prevalence and mechanisms of selfish DNA transmission in mammals.
Generation of Gene Drive Mice for Invasive Pest Population Suppression
22890M. D. Bunting, C. Pfitzner, L. Gierus, M. White, S. Piltz and P. Q. Thomas, Applications of Genome Modulation and Editing, 2022-06-14 06:00:54.
Gene drives are genetic elements that are transmitted to greater than 50% of offspring and have potential for population modification or suppression. While gene drives are known to occur naturally, the recent emergence of CRISPR-Cas9 genome-editing technology has enabled generation of synthetic gene drives in a range of organisms including mosquitos, flies, and yeast. For example, studies in Anopheles mosquitos have demonstrated >95% transmission of CRISPR-engineered gene drive constructs, providing a possible strategy for malaria control. Recently published studies have also indicated that it may be possible to develop gene drive technology in invasive rodents such as mice. Here, we discuss the prospects for gene drive development in mice, including synthetic “homing drive” and X-shredder strategies as well as modifications of the naturally occurring t haplotype. We also provide detailed protocols for generation of gene drive mice through incorporation of plasmid-based transgenes in a targeted and non-targeted manner. Importantly, these protocols can be used for generating transgenic mice for any project that requires insertion of kilobase-scale transgenes such as knock-in of fluorescent reporters, gene swaps, overexpression/ectopic expression studies, and conditional “floxed” alleles.
A meiotic driver alters sperm form and function in house mice: a possible example of spite
22697L. Winkler and A. K. Lindholm, Chromosome Research, 2022-06-01 14:48:38.
The ability to subvert independent assortment of chromosomes is found in many meiotic drivers, such as the t haplotype in house mice Mus musculus, in which the t-bearing chromosomal homolog is preferentially transmitted to offspring. This is explained by a poison-antidote system, in which developing + and t sperm in testes of + /t males are exposed to 'poison' coded by t loci, from which t sperm are protected, allowing t sperm an overwhelming fertilisation advantage in monogamous matings. This system is thought to result in poorly and normally motile sperm subpopulations within + /t sperm, leaving t sperm unharmed. Conversely, we found that the fastest quartile of sperm from + /t males swam more slowly, both forwards and along their travel path, and had reduced straightness and linearity, compared to the fastest quartile of + / + sperm. Moreover, sperm from + /t males had shorter tails and narrower heads than + / + sperm, and these morphological differences covaried with motility differences. Finally, + /t traits did not show evidence of bimodal distributions. We conclude that the t haplotype drive results in lasting damage to the motility of both + and t developing sperm, although previous studies indicate that + must be more harmed than t sperm. This damage to all sperm may explain the low success of + /t males in sperm competition with + / + males, seen in earlier studies. We propose that the harm the t causes to itself could be termed 'spiteful', which may also be common to other gamete-harming meiotic drive systems.
Bayesian network-based risk assessment of synthetic biology: Simulating CRISPR-Cas9 gene drive dynamics in invasive rodent management
22516E. A. Brown, S. R. Eikenbary and W. G. Landis, Risk Analysis, 2022-05-14 07:22:34.
Gene drive technology has been proposed to control invasive rodent populations as an alternative to rodenticides. However, this approach has not undergone risk assessment that meets criteria established by Gene Drives on the Horizon, a 2016 report by the National Academies of Sciences, Engineering, and Medicine. To conduct a risk assessment of gene drives, we employed the Bayesian network-relative risk model to calculate the risk of mouse eradication on Southeast Farallon Island using a CRISPR-Cas9 homing gene drive construct. We modified and implemented the R-based model "MGDrivE" to simulate and compare 60 management strategies for gene drive rodent management. These scenarios spanned four gene drive mouse release schemes, three gene drive homing rates, three levels of supplemental rodenticide dose, and two timings of rodenticide application relative to gene drive release. Simulation results showed that applying a supplemental rodenticide simultaneously with gene drive mouse deployment resulted in faster eradication of the island mouse population. Gene drive homing rate had the highest influence on the overall probability of successful eradication, as increased gene drive accuracy reduces the likelihood of mice developing resistance to the CRISPR-Cas9 homing mechanism.
Selfish migrants: How a meiotic driver is selected to increase dispersal
20575J. N. Runge, H. Kokko and A. K. Lindholm, J Evol Biol, 2022-03-07 10:54:44.
Meiotic drivers are selfish genetic elements that manipulate meiosis to increase their transmission to the next generation to the detriment of the rest of the genome. One example is the t haplotype in house mice, which is a naturally occurring meiotic driver with deleterious traits-poor fitness in polyandrous matings and homozygote inviability or infertility-that prevent its fixation. Recently, we discovered and validated a novel effect of t in a long-term field study on free-living wild house mice and with experiments: t-carriers are more likely to disperse. Here, we ask what known traits of the t haplotype can select for a difference in dispersal between t-carriers and wildtype mice. To that end, we built individual-based models with dispersal loci on the t and the homologous wildtype chromosomes. We also allow for density-dependent expression of these loci. The t haplotype consistently evolves to increase the dispersal propensity of its carriers, particularly at high densities. By examining variants of the model that modify different costs caused by t, we show that the increase in dispersal is driven by the deleterious traits of t, disadvantage in polyandrous matings and lethal homozygosity or male sterility. Finally, we show that an increase in driver-carrier dispersal can evolve across a range of values in driver strength and disadvantages.
Could we delete diseases passed down through our DNA?
20278E. Rayne, SYFY, 2022-01-23 11:33:23.
What has now been proven possible was once the stuff of science fiction dreams. CRISPR has shown it can successfully edit out detrimental genetic conditions before they are inherited — which could mean the beginning of the end for hereditary diseases. It could also help obliterate invasive species from ecosystems under attack. Imagine if gene editing could delete conditions you never asked to be born with while getting rid of the cane toad invasion in Australia. CRISPR-Cas9 has been able to successfully edit DNA again and again, but it’s never done anything like this. Kind of like DNA autocorrecting itself, the editing needs to make deletion in a cell happen during a certain phase of meiosis. Researcher Kimberly Cooper of UC San Diego, who coauthored a study recently published in PLOS Biology, figured out exactly when to get to that meiotic window and how to control which copies of genes are handed down to the next generation.
Scientists expand CRISPR-Cas9 genetic inheritance control in mammals
20038M. Aguilera, Phys Org, 2022-01-12 09:43:07.
Led by graduate student Alexander Weitzel, Grunwald, Cooper and their colleagues have now succeeded in developing CRISPR-Cas9 inheritance control in male mice by shifting the gene editing window to more closely match the timing of meiosis in both sexes. Their results were published December 23, 2021 in the journal PLOS Biology. The achievement advances the prospects of scientists being able to use genetic editing for new laboratory models in an array of research pursuits, from investigations of human disease to therapeutic drug design to invasive species removal. "For these gene conversion strategies to work in any context—in the lab or in wild populations—you need the mechanism of gene conversion to work in both males and females," said Cooper, associate professor in the Section of Cell and Developmental Biology, Division of Biological Sciences. "It seems as though the reason this process was previously working in females is because we were closer to the female meiotic window. Now that we've moved Cas9 expression to within the meiotic window in males, it works in them too."
Modeling CRISPR gene drives for suppression of invasive rodents using a supervised machine learning framework
19764S. E. Champer, N. Oakes, R. Sharma, P. García-Díaz, J. Champer and P. W. Messer, PLoS Comput Biol, 17:e1009660. 2021-12-29 13:01:20.
Invasive rodent populations pose a threat to biodiversity across the globe. When confronted with these invaders, native species that evolved independently are often defenseless. CRISPR gene drive systems could provide a solution to this problem by spreading transgenes among invaders that induce population collapse, and could be deployed even where traditional control methods are impractical or prohibitively expensive. Here, we develop a high-fidelity model of an island population of invasive rodents that includes three types of suppression gene drive systems. The individual-based model is spatially explicit, allows for overlapping generations and a fluctuating population size, and includes variables for drive fitness, efficiency, resistance allele formation rate, as well as a variety of ecological parameters. The computational burden of evaluating a model with such a high number of parameters presents a substantial barrier to a comprehensive understanding of its outcome space. We therefore accompany our population model with a meta-model that utilizes supervised machine learning to approximate the outcome space of the underlying model with a high degree of accuracy. This enables us to conduct an exhaustive inquiry of the population model, including variance-based sensitivity analyses using tens of millions of evaluations. Our results suggest that sufficiently capable gene drive systems have the potential to eliminate island populations of rodents under a wide range of demographic assumptions, though only if resistance can be kept to a minimal level. This study highlights the power of supervised machine learning to identify the key parameters and processes that determine the population dynamics of a complex evolutionary system.
Meiotic Cas9 expression mediates gene conversion in the male and female mouse germline
19726A. J. Weitzel, H. A. Grunwald, C. Weber, R. Levina, V. M. Gantz, S. M. Hedrick, E. Bier and K. L. Cooper, PLOS Biology, 19:e3001478. 2021-12-23 12:46:23.
Highly efficient gene conversion systems have the potential to facilitate the study of complex genetic traits using laboratory mice and, if implemented as a “gene drive,” to limit loss of biodiversity and disease transmission caused by wild rodent populations. We previously showed that such a system of gene conversion from heterozygous to homozygous after a sequence targeted CRISPR/Cas9 double-strand DNA break (DSB) is feasible in the female mouse germline. In the male germline, however, all DSBs were instead repaired by end joining (EJ) mechanisms to form an “insertion/deletion” (indel) mutation. These observations suggested that timing Cas9 expression to coincide with meiosis I is critical to favor conditions when homologous chromosomes are aligned and interchromosomal homologydirected repair (HDR) mechanisms predominate. Here, using a Cas9 knock-in allele at the Spo11 locus, we show that meiotic expression of Cas9 does indeed mediate gene conversion in the male as well as in the female germline. However, the low frequency of both HDR and indel mutation in both male and female germlines suggests that Cas9 may be expressed from the Spo11 locus at levels too low for efficient DSB formation. We suggest that more robust Cas9 expression initiated during early meiosis I may improve the efficiency of gene conversion and further increase the rate of “super-mendelian” inheritance from both male and female mice.
How sci-fi weapon could stop grey squirrels killing Britain’s trees
19723rymeradelle, INentertainment, 2021-12-23 12:41:06.
Grey squirrels pose the greatest threat to British foresters at the moment. They eat the bark of trees, leaving them to die. Picture: Grey squirrel perched on a tree It’s bad enough watching Britain’s ash trees wither from the ash dieback fungus now ravaging our countryside. We can only do so much. The squirrel is an exception to this rule. And it’s not just trees which are paying the price. This pest kills songbirds, and also pinches nests. Worse still, our native red squirrel, which once roamed the entire country — without chewing trees to death — is now an endangered species, clinging on in pockets of Scotland and places such as the Isle of Wight. The number of people living in the area is estimated to be around 200,000. Red Squirrel Survival Trust will make an announcement next month, with Red Squirrel Day on January 21. Its patron, the Prince of Wales, loves the vanishing red so much that he has a squirrel-feeding table in the hallway at Birkhall, his home on the Balmoral estate (where he has also erected ‘Squirrel Crossing’ road signs).
Scientists Used CRISPR Gene Editing to Choose the Sex of Mouse Pups
19906S. Fan, Singuarity Hub, 2021-12-23 08:37:01.
“Do you want a boy or a girl?” can be an awkward question.But in certain circles, it’s a question that’s asked every day. Take agriculture. In a perfect world, most cows would only birth females. Chicks would grow up to be all hens. “Sexing” a farm animal when they’re at a young age wouldn’t be a thing—especially when it means male animals, without the ability to produce milk or eggs, are often culled at a young age to preserve resources. There might be a better way. This month, a team tapped into the power of CRISPR to control the sex of the offspring in mice. By splicing CRISPR components into the parents’ genome, the team was able to flip on—or off—a switch that nearly perfectly determined the sex of their litters. Unlike previous attempts, the baby mice could go on to have litters of their own of both sexes. The targeted gene used for the edit is conserved across evolution, suggesting the technique could work in more animals than just mice. But it’s controversial. Essentially, the technique selectively kills off embryos of a certain sex, which immediately raises ethical red flags. For now, scientists aren’t concerned about the technology being used in humans due to its complexity. But the study is the latest to showcase biotech’s increasing ability to manipulate reproduction.
Gene editing used to create all-male or all-female litters of mice
19542J. Goodyer, Science Focus, 2021-12-06 20:26:39.
As males are unable to produce milk or lay eggs, the ability to breed cows and hens that produce all-female litters is likely to be high on most poultry and dairy farmers’ wish lists. Now, scientists at the Francis Crick Institute and the University of Kent have come a step closer to realising this goal after successfully using CRISPR gene editing techniques to produce all-female or all-male litters of mice. The technique could also be used to improve animal welfare in areas of scientific research in which only male or only female animals are required for studies, the researchers say. To make the breakthrough the researchers took advantage of the fact that CRISPR consists of two parts – the Cas9 enzyme, which cuts the DNA and enables scientists to alter specific regions of genes, and the guide RNA, which carries the Cas9 enzyme to the desired region on the genome.
Gene editing used to create all-male or all-female mice litters
19502A. Reis, European Scientist, 2021-12-04 17:04:50.
Researchers from the Francis Crick Institute and the University of Kent used gene-editing technologies to create male-only and female-only mice litters, according to a study published in Nature Communications (1). The authors also suggested ways in which this method could be used to improve animal welfare in scientific research and agriculture. There are many situations in research and agriculture where it would be desirable to have just females or just males. For example, reproductive studies require only animals of the gender being studied, while in farming, egg and milk production needs only female animals. Sadly, in many cases, the unwanted animals end up being culled. “This work could have an immediate and valuable impact in scientific laboratories, as we’ve shown how it is safe and effective in mice, a common mammal used in medical and scientific research. While a lot of research needs both sexes, there are areas of study where only one is needed. For example, when studying the reproductive system, sex-specific diseases, or certain hormones”, said James Turner, group leader of the Sex Chromosome Biology Laboratory at the Crick says:
Gene-editing used to create single sex mice litters
19504The Francis Crick Institute, Phys Org, 2021-12-03 17:09:04.
Scientists at the Francis Crick Institute, in collaboration with University of Kent, have used gene editing technology to create female-only and male-only mice litters with 100% efficiency. This proof of principle study, published in Nature Communications today, demonstrates how the technology could be used to improve animal welfare in scientific research and perhaps also agriculture. In scientific research and also farming, there is often a need for either male or female animals. For example, laboratory research into male or female reproduction requires only animals of the sex being studied. And in farming, only female animals are required for egg production and in dairy herds. This means it is common practice for animals of the unrequired sex to be culled after birth. The researchers' new method uses a two-part genetic system to inactivate embryos shortly after fertilisation, allowing only the desired sex to develop. Such a genetically-based method to control the sex of offspring could drastically reduce culling in both industries. The embryo selection is based on the fact that there are two elements of CRISPR-Cas9—the Cas9 enzyme that cuts the DNA, allowing scientists to alter specific regions, and the guide RNA which carries the Cas9 to the right location on the genome. The team placed one element of the system on the father's X or Y chromosome, meaning that it will only be inherited by female or male embryos respectively. The other element is contributed by the mother, and is inherited by all embryos.
Single-sex mice litters were created with 100% efficiency using gene editing.
19498R. Silman, Brinkwire, 2021-12-03 17:00:12.
The Francis Crick Institute, in partnership with the University of Kent, has employed gene editing technology to construct 100% efficient female-only and male-only mouse litters. This proof-of-concept study, which was published today (Friday, December 3rd, 2021) in Nature Communications, shows how the technique could be used to improve animal wellbeing in scientific research and possibly agriculture. Male and female animals are frequently required in scientific research and husbandry. Laboratory research into male or female reproduction, for example, necessitates only animals of the examined sex. In addition, only female animals are needed for egg production and dairy herds in farming. This means that animals of the unrequired sex are routinely culled after birth.
Lab animals: Gene-editing technology is used to create female-only and male-only mice litters
19493todayuknews, Today UK News, 2021-12-03 16:50:32.
Single-sex litters of mice — comprising only either female or male pups — have been produced by means of so-called CRISPR-Cas9 gene editing technology. The technique, developed by experts at the Francis Crick Institute and the University of Kent, works by inactivating embryos of one sex shortly after fertilisation. It could be used to improve animal welfare in both laboratory and agricultural settings where, for various reasons, only female or male animals are needed. It is common for animals of the unrequired sex to be culled — a practice which could be drastically reduced by controlling the sex of the animals prior to birth. As the technique requires the genetic modification of both parents to work, however, the approach would not be suitable for forcing the sex of designer babies. Single-sex litters of mice — comprising only either female or male pups — have been produced by means of so-called CRISPR-Cas9 gene editing technology. Pictured: the mice that were bred to create single-sex litters. The black parts of their coat are caused by the genetically modified cells, while the white parts come from the non-modified parts of their genome
Gene editing produces all-male or all-female litters of mice
19491E. Pennisi, Science, 2021-12-03 16:41:41.
In some farmers’ ideal world, cows would birth only females, sows would bear no boars, and chicks would all grow up to be hens. Such sex ratios would stop them from killing millions of male animals, which don’t produce eggs or milk. Now, scientists are a step closer to this reality. Researchers have harnessed the gene editor CRISPR to produce litters of mice all of one sex. That’s a potential boon to agriculture and may offer a more immediate advantage in scientific research. “The paper shows a state-of-the-art solution to producing single-sex species,” with “impressive results,” says Ehud Qimron, a CRISPR expert at Tel Aviv University who was not involved with the work. The impact for lab animals may be huge. “In the past 5 years around 25,000 papers were published using mice in sex-specific research studies,” says study co-author James Turner, a molecular geneticist at the Francis Crick Institute. “If we could prevent the generation of the unstudied sex, the number [saved] would be in the hundreds of thousands.” Other methods exist to skew the male/female ratio of newborn animals. Scientists can sort sperm by the weight of the sex chromosome, or cause embryos of one sex to die before birth. In a study published 2 years ago, researchers using the gene editor CRISPR managed to produce altered mice in which four of five litters were all female.
CRISPR-Cas9 effectors facilitate generation of single-sex litters and sex-specific phenotypes
19469C. Douglas, V. Maciulyte, J. Zohren, D. M. Snell, S. K. Mahadevaiah, O. A. Ojarikre, P. J. I. Ellis and J. M. A. Turner, Nature Communications, 12:6926. 2021-12-03 15:06:30.
Animals are essential genetic tools in scientific research and global resources in agriculture. In both arenas, a single sex is often required in surplus. The ethical and financial burden of producing and culling animals of the undesired sex is considerable. Using the mouse as a model, we develop a synthetic lethal, bicomponent CRISPR-Cas9 strategy that produces male- or female-only litters with one hundred percent efficiency. Strikingly, we observe a degree of litter size compensation relative to control matings, indicating that our system has the potential to increase the yield of the desired sex in comparison to standard breeding designs. The bicomponent system can also be repurposed to generate postnatal sex-specific phenotypes. Our approach, harnessing the technological applications of CRISPR-Cas9, may be applicable to other vertebrate species, and provides strides towards ethical improvements for laboratory research and agriculture.
Transmission distortion and genetic incompatibilities between alleles in a multigenerational mouse advanced intercross line
19320D. Arends, S. Kärst, S. Heise, P. Korkuc, D. Hesse and G. A. Brockmann, Genetics, 2021-11-15 14:07:56.
While direct additive and dominance effects on complex traits have been mapped repeatedly, additional genetic factors contributing to the heterogeneity of complex traits have been scarcely investigated. To assess genetic background effects, we investigated transmission ratio distortions (TRDs) of alleles from parent to offspring using an advanced intercross line (AIL) of an initial cross between the mouse inbred strains C57BL/6NCrl (B6N) and BFMI860-12 (BFMI). 341 males of generation 28 and their respective 61 parents and 66 grandparents were genotyped using Mega Mouse Universal Genotyping Arrays (MegaMUGA). TRDs were investigated using allele transmission asymmetry tests, and pathway overrepresentation analysis was performed. Sequencing data was used to test for overrepresentation of non-synonymous SNPs in TRD regions. Genetic incompatibilities were tested using the Bateson-Dobzhansky-Muller two-locus model. 62 TRD regions were detected, many in close proximity to the telocentric centromere. TRD regions contained 44.5% more non-synonymous SNPs than randomly selected regions (182 vs. 125.9 ± 17.0, P < 1x10-4). Testing for genetic incompatibilities between TRD regions identified 29 genome-wide significant incompatibilities between TRD regions (P(BF) < 0.05). Pathway overrepresentation analysis of genes in TRD regions showed that DNA methylation, epigenetic regulation of RNA, and meiotic/meiosis regulation pathways were affected independent of the parental origin of the TRD. Paternal BFMI TRD regions showed overrepresentation in the small interfering RNA (siRNA) biogenesis and in the metabolism of lipids and lipoproteins. Maternal B6N TRD regions harbored genes involved in meiotic recombination, cell death, and apoptosis pathways. The analysis of genes in TRD regions suggests the potential distortion of protein-protein interactions influencing obesity and diabetic retinopathy as a result of disadvantageous combinations of allelic variants in Aass, Pgx6 and Nme8. Using an AIL significantly improves the resolution at which we can investigate TRD. Our analysis implicates distortion of protein-protein interactions as well as meiotic drive as the underlying mechanisms leading to the observed TRD in our AIL. Furthermore, genes with large amounts of non-synonymous SNPs located in TRD regions are more likely to be involved in pathways that are related to the phenotypic differences between the parental strains. Genes in these TRD regions provide new targets for investigating genetic adaptation, protein-protein interactions, and determinants of complex traits such as obesity.
To exterminate, or not to: Scientists debate tweaking wild genomes
18529French Press Agency, Daily Sabah, 2021-09-12 16:11:31.
veryone remembers Jeff Goldblum's famous speech in 1993 classic Jurassic Park: “Your scientists were so preoccupied with whether they could, they didn't stop to think if they should.” Well, these scientists are debating whether one should. In the movie, reconstructing and tweaking genetic material had made it possible to bring dinosaurs back to life. Today, a technology that manipulates animal genomes, called gene drive, has become a reality. The goal, however, is not to revive long-gone species, but to eliminate invasive ones. Steven Spielberg's film was set on an imaginary island off the coast of Costa Rica, and it is also on an island that the first open-air experiments in programmed extinction could take place, according to experts gathered at the International Union for the Conservation of Nature (IUCN) Congress in Marseille. It could happen within a decade, they told Agence France-Presse (AFP). That's because fragile island ecosystems are in crisis. Dozens of vertebrate species have vanished in the last century, and dozens more are on a glide path to extinction. The culprits are non-native rats, snakes and mosquitoes – all introduced by humans, for the most part by accident – that eat bird eggs, infect birds with disease, or outcompete indigenous amphibians and mammals. For more than 20 years, Island Conservation has been working to eradicate rodents and other invasive alien species, which are a major threat to biodiversity globally, the organization's Royden Saah told AFP. The conservation NGO has been successful on two Galapagos islands – Seymour North and Mosquera – using traps and poison-delivering drones. But species eradication using these tools is costly and has no guarantee of success. Rat poison is effective, but poses risks to other species.
Scientists debate promise, peril of tweaking wild genomes
18517J. Zamora, Phys Org, 2021-09-11 14:53:57.
In the movie Jurassic Park, reconstructing and tweaking genetic material makes it possible to bring dinosaurs back to life. Today, a technology that manipulates animal genomes, called gene drive, has become a reality. The goal, however, is not to revive long-gone species, but to eliminate invasive ones. Steven Spielberg's film was set on an imaginary island off the coast of Costa Rica, and it is also on an island that the first open-air experiments in programmed extinction could take place, according to experts gathered at the International Union for the Conservation of Nature (IUCN) Congress in Marseille. It could happen within a decade, they told AFP. That's because fragile island ecosystems are in crisis. Dozens of vertebrate species have vanished in the last century, and dozens more are on a glide path to extinction. The culprits are non-native rats, snakes and mosquitoes—all introduced by humans, for the most part by accident—that eat bird eggs, infect birds with disease, or outcompete indigenous amphibians and mammals.
$1M in funding for project to cull mouse plagues
18349K. Brown, University of Adelaide NEWSROOM, 2021-08-31 13:47:59.
South Australian researchers are set to use genetic tools to help find innovative solutions to the devastating mouse plagues that have caused massive economic damage to Australian farmers.The University of Adelaide has been awarded $1 million in funding from the South Australian Government’s Research and Innovation Fund (RIF), to undertake the ground-breaking Genetic Biocontrol Technology for Invasive Pests, or Gene Drive, project, in conjunction with the Department for Environment and Water.Researchers from the University of Adelaide will develop genetic strategies to suppress invasive rodents with maximum specificity and safety. The team will also conduct research to engage with stakeholders to understand community views and concerns.
GeneConvene Global Collaborative Webinar Series | Invasive Species Management: Informing Gene Drive Considerations
19307David O'Brochta and Hector Quemada, GeneConvene Global Collaborative, 2021-08-07 13:38:24.
The management, control and elimination of invasive species involves solving problems that have analogs to those anticipating the use of gene drive technologies to control and eliminate malaria in Africa. Avoiding unintended consequences from interventions designed to reduce or remove a species from an ecosystem has parallels in some applications of gene drive technologies. Monitoring and surveilling for the movement of invasive species is critical for making management decisions and methods and approaches that have been devised to deal with challenges such as large geographic areas, low species densities, limited resources to name just a few could inform thinking about monitoring and surveillance of gene drive-containing organisms. This series of webinars by invasive species specialists will feature research into how these challenges are being successfully addressed.
Mice Plague Eastern Australia in Record Numbers
17751B. Nogrady, The Scientist, 2021-07-12 13:50:17.
Just before Christmas last year, Julie Leven and her husband Des took their camper up to visit their son in northern New South Wales, Australia. Driving back at night to their home in Gilgandra, around 430 kilometers northwest of Sydney, they saw masses of white spots moving across the dark road surface. The spots, they soon realized, were mice. Once they reached their house, the Levens saw a scene of rodent devastation. Mice had invaded their home in such numbers that it was unlivable. The creatures had gnawed their way into the pantry and ruined all the food they could get into. Their droppings and pungent urine were spread from one end of the dwelling to the other, across soft furnishings and bedding. The rodents had even eaten the insulation around the engine wiring in two tractors and ruined their harvested hay bales.
Patterns and Mechanisms of Sex Ratio Distortion in the Collaborative Cross Mouse Mapping Population
17511B. A. Haines, F. Barradale and B. L. Dumont, bioRxiv, 2021-06-23 14:26:09.
In species with single-locus chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, are not fully mediated by maternal effects, and are not explained by sex-biased neonatal mortality. SRD exhibits a heritable component, but QTL mapping analyses and targeted investigations of sex determination genes fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We speculate that the genetic shuffling of eight diverse parental genomes during the early CC breeding generations led to the decoupling of sex-linked drivers from their co-evolved suppressors, unleashing complex, multiallelic systems of sex chromosome drive. Consistent with this interpretation, we show that several CC strains exhibit copy number imbalances at co-evolved X- and Y-linked ampliconic genes that have been previously implicated in germline genetic conflict and SRD in house mice. Overall, our findings reveal the pervasiveness of SRD in the CC population and nominate the CC as a powerful resource for investigating sex chromosome genetic conflict in action.
Selfish DNA: how new gene technology could stop the advance of mice
17450M. McMillan, Tentenfield Star, 2021-06-15 17:20:08.
It used to be that seeing a mouse in the house was a rare occurrence. Now, it's rarely a day that goes by where we aren't seeing or hearing the little vermin. Current methods of baiting and trapping are struggling to control the plague of mice spreading across regional Australia. But a $1.8 million investment from the NSW government might soon give us a new weapon in the war. The government is investing in research into the use of gene drives, or "selfish DNA" - a genetic tool that can help us to control pests. How? Well, to understand gene drives we first need to understand the normal way in which genes are inherited. Mice, like humans, have two copies of each gene, one inherited from their mother and one from their father. We call these copies alleles, and they can be exactly the same or slightly different from each other. Normally, there is a 50/50 chance as to which allele will be passed on to any offspring. If one allele carries some sort of mutation, there is a 50 per cent chance that it will be passed on.
Victory: NSW Government Invests in Humane Mice Control!
17224PETA Australia, PETA Australia, 2021-06-05 16:21:19.
Just two weeks after calling us “brainless” for suggesting that the state government invest in more ethical, eco-friendly methods of mice control – Minister for Agriculture Adam Marshall announced a $1.8 million package to “fast-track the delivery of next generation ‘gene drive’ technology to control future plagues”. The money will fund a three-year programme of genetic biocontrol research, led by the University of Adelaide, CSIRO, and the Centre for Invasive Species Solutions, to identify fast-acting gene drives designed to spread an inherited characteristic through a population. The research will test two strategies for population control, including an approach which eliminates sperm carrying the X chromosome, producing more male than female offspring, and a second approach of making female mice infertile. PETA has been talking about immunocontraception methods of controlling invasive animal populations for years, so we’re pleased to see the government is finally using science to tackle this problem in a more ethical and eco-friendly manner. Had it acted sooner, millions of small animals, including non-target species, would have been spared slow and agonising deaths. Last month, the New South Wales government announced it would use a new, strong poison and spruiked it as “napalm” for mice. Leading rodent experts questioned the plan, warning that the poison’s use came with a high risk of killing native and domestic animals as well. Dr Peter Brown, leader of the rodent management research team at CSIRO, told The Guardian, “The anti-coagulants can accumulate up through the food chain, and so birds of prey or other animals can be feeding on dead mice and they could potentially get a lethal dose themselves through secondary poisoning.”
New biocontrol research to help prevent mice plagues
17206Anonymous, The National Tribune, 2021-06-04 15:41:51.
Scientists at the University of Adelaide are partnering with the CSIRO and the Centre for Invasive Species Solutions on breakthrough genetic biocontrol research to help control mice populations and prevent future mice plagues. The three-year research program will identify fast acting gene drives, which are designed to spread an inherited characteristic for population control through mice populations at higher-than-normal rates. This would effectively enable scientists to interrupt the breeding cycle and keep mice populations at manageable levels. The NSW Government will provide $1.8 million towards the project to fast-track the delivery of the ‘gene drive technology’ as part of a range of measures not only to mitigate the impacts of the mice currently across NSW, but also to create options to reduce the impact of future population spikes.
Gene drive could be a game changer for future mouse control.
17214Anonymous, Centre for Invasive Species Solutions, 2021-06-03 16:02:28.
We are proud to announce we will be coordinating a brand new, three-year program of genetic biocontrol research, which will identify fast acting gene drives designed to spread an inherited characteristic through a population at higher-than-normal rates. Using targeted gene drives, scientists aim to interrupt the breeding cycle of mice and potentially other ferals, which could keep populations at manageable levels. The $1.8 million research program will be led by Professor Paul Thomas at our partner organisation the University of Adelaide in collaboration with our member organisation CSIRO. The NSW Minister for Agriculture, Adam Marshall said cutting edge solutions meant future mouse plagues could be extinguished before they begin. This specific research funding will test two strategies for population control and recommend at least one for future suppression of mice. The ‘X-shredder’ approach eliminates sperm carrying the X chromosome, producing more male than female offspring. The ‘female infertility’ approach spreads a genetic modification that would eventually make females infertile. We look forward to seeing the outcomes of this world-class innovative research being led by Aussie scientists.
“Gene Drive” Technology To Control Mouse Invasions | Liverpool City Champion
17208T. Carrington, Liverpool IL, 2021-06-03 15:45:57.
As western New South Wales faces a devastating mouse plague, the government is investing in groundbreaking genetic biocontrol research that could transform pest management in Australia. Agriculture Minister Adam Marshall said the NSW government will provide $ 1.8 million for the project to accelerate delivery of next-generation ‘gene drive’ technology to control future plagues. “The government has invested $ 50 million in a range of supportive measures, not only to mitigate the impacts of the mice that are currently crawling across much of New South Wales, but also to create options to reduce l ‘impact of future population peaks, “he said. Thursday. Until now, farmers had to rely on baiting and trapping to control mouse infestations, but the government is now “accelerating critical research to bring mouse control into the 21st century,” he said. declared. The three-year genetic biocontrol research program will identify fast-acting gene drives that are designed to spread an inherited trait through a population at above normal rates.
Australia plots biological warfare to eradicate rampaging ‘mouse plague’
17204J. Smyth, Financial Times, 2021-06-03 15:37:11.
Australia is home to some of the world’s most fearsome creatures. But none is more destructive than the humble house mouse, a plague of which is rampaging across vast swaths of farmland and terrorising countryfolk. Farmers in New South Wales, the worst affected state, warned the furry critters could cost them A$1bn ($765m) in lost crops and poison baits this season. Residents in rural towns have been fighting a six-month battle against the army of wild house mice, which has gnawed through wiring on home appliances, polluted water supplies and even bitten patients in hospital beds. Scientists said the plague was bolstered by favourable weather conditions after years of drought and the nation’s second biggest grain harvest on record. State authorities have proposed “napalming” the mice by allowing farmers to use the poison bromadiolone against the mice, which has ignited a furious debate over its environmental impact.
Mouse plague control hopes raised with funding for genetic biocontrol research
17289Anonymous, From Press, 2021-06-03 10:36:25.
As communities and farmers continue to battle the mouse plague, a funding announcement for genetic biocontrol research could be a potential game changer for future plagues. The New South Wales government has today announced a $50 million mouse control package which includes $1.8 million dollars in funding for genetic control of mice populations. The project aims to fast-track the delivery of next generation "gene drive" technology to control plagues of the future. Researchers have welcomed the announcement, including Australia's lead researcher Professor Paul Thomas from the University of Adelaide. He said the technology is only relatively new, having been developed to some extent for insects and malaria control, but has not yet been applied to mammals. "So effectively it just uses the natural mating processes to spread a gene though a population that will cause, [and] what we are trying to cause, female [mouse] infertility," he said. "We have modelled it already and that should cause the population to crash over time. "This boost of funding will enable us to move much faster on these projects."Another control approach will also be investigated, the "X-shredder" approach, which eliminates sperm carrying the X chromosome, producing more male than female offspring.
‘Gene drive’ tech to control mice plagues
17219AAP, Countryman, 2021-06-02 16:11:50.
As western NSW deals with a devastating mouse plague the government is investing in breakthrough genetic biocontrol research that could transform pest management in Australia. Agriculture Minister Adam Marshall said the NSW government would provide $1.8 million to the project to fast-track the delivery of next generation 'gene drive' technology to control future plagues. "The government has invested $50 million in a range of support measures, not only to mitigate the impacts of the mice currently crawling across so much of NSW, but also to create options to ensure we reduce the impact of future population spikes," he said on Thursday. Until now farmers have had to rely on baiting and trapping to control mouse infestations but the government was now "fast-tracking critical research to bring mouse control into the 21st century", he said. The three-year program of genetic biocontrol research will identify fast acting gene drives which are designed to spread an inherited characteristic through a population at higher-than-normal rates. Mr Marshall said it would also investigate the transferability of the technology to other pest species such as black rats, rabbits and feral cats using advanced computer modelling.
Scientists want to alter rodent genes to prevent mice plagues
17092P. Hannon, The Sydney Morning Herald, 2021-05-23 10:52:32.
Mice plagues, such as the one ravaging parts of inland NSW, could become a thing of the past if scientists succeed in modifying the genes of the rodents so that populations crash before they can take off. Paul Thomas, a researcher at the University of Adelaide, is part of an international consortium including the CSIRO and the US Department of Agriculture, studying how to safely alter genes to make female mice infertile. The techniques learned could potentially be applied to other damaging invasive mammals such as cats and foxes.
Experiments confirm a dispersive phenotype associated with a natural gene drive system
17036J.-N. Runge and A. K. Lindholm, Royal Society Open Science, 8:202050. 2021-05-12 11:24:14.
Meiotic drivers are genetic entities that increase their own probability of being transmitted to offspring, usually to the detriment of the rest of the organism, thus ‘selfishly’ increasing their fitness. In many meiotic drive systems, driver-carrying males are less successful in sperm competition, which occurs when females mate with multiple males in one oestrus cycle (polyandry). How do drivers respond to this selection? An observational study found that house mice carrying the t haplotype, a meiotic driver, are more likely to disperse from dense populations. This could help the t avoid detrimental sperm competition, because density is associated with the frequency of polyandry. However, no controlled experiments have been conducted to test these findings. Here, we confirm that carriers of the t haplotype are more dispersive, but we do not find this to depend on the local density. t-carriers with above-average body weight were particularly more likely to disperse than wild-type mice. t-carrying mice were also more explorative but not more active than wild-type mice. These results add experimental support to the previous observational finding that the t haplotype affects the dispersal phenotype in house mice, which supports the hypothesis that dispersal reduces the fitness costs of the t.
Meiotic Cas9 expression mediates genotype conversion in the male and female mouse germline.
16618A. J. Weitzel, H. A. Grunwald, R. Levina, V. M. Gantz, S. M. Hedrick, E. Bier and K. L. Cooper, 2021.03.16.435716, 2021-03-17 17:52:21.
We previously showed that such a system of genotype conversion from heterozygous to homozygous after a sequence targeted CRISPR/Cas9 double strand DNA break is feasible in the female mouse germline. In the male germline, however, all double strand breaks were instead repaired by end joining mechanisms to form an 'insertion/deletion' (indel) mutation. These observations suggested that timing Cas9 expression to coincide with meiosis I is critical to favor conditions when homologous chromosomes are aligned and interchromosomal homology directed repair (HDR) mechanisms predominate. Here, using a Cas9 knock-in allele at the Spo11 locus, we show that meiotic expression of Cas9 does indeed mediate genotype conversion in the male as well as in the female germline. However, the low frequency of both HDR and indel mutation in both male and female germlines suggests that Cas9 may be expressed from the Spo11 locus at levels too low for efficient double strand DNA break formation. We suggest that more robust Cas9 expression initiated during early meiosis I may improve the efficiency of genotype conversion and further increase the rate of 'super-Mendelian' inheritance from both male and female mice.Competing Interest StatementVMG, SMH, EB, and KLC hold advisory board positions with Synbal, Inc. All other authors declare that they have no competing interests.
Gene-Editing Approach To Control the Invasive Gray Squirrel
16572M. Campbell, Technology Networks, 2021-03-08 14:33:09.
Biodiversity refers to the extent of the variety of life that is found on planet Earth – and it is currently under threat. Changes in biodiversity have been flagged as "surpassing safe limits" for several years, and world leaders and scientists across the globe are consequently exploring different ways to address the crisis. Invasive species, defined by National Geographic as "an organism that is not indigenous, or native, to a particular area", threaten planet Earth's biodiversity to an even greater extent than climate change. The Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) Global Assessment Report found that the number of invasive species per country have risen by ~70% since 1970 across 21 countries that were included in the report. An example of an invasive species is the gray squirrel Sciurus carolinensis found in the UK, which outcompetes the native red squirrel for resources and habitats and carries diseases that are not pathogenic to themselves but can kill red squirrels.
Ecology: Gene drives may help control invasive grey squirrel in the UK
16557A. Korn, EurekaAlert, 2021-03-04 19:50:50.
Gene drives introduce genes into a population that have been changed to induce infertility in females, allowing for the control of population size. However, they face technical challenges, such as controlling the spread of altered genes as gene drive individuals mate with wild individuals, and the development of genetic resistance, which may render the gene drive ineffective. To address these challenges, Nicky Faber and colleagues used computer modelling to investigate the effectiveness of a combination of three gene drive technologies using the grey squirrel as a case study.
Genetically modified squirrels could curb growing population of greys
16542S. Knapton, Telegraph, 2021-03-04 16:06:59.
Mutant grey squirrels, genetically modified to spread infertility genes, could be released into the wild to tackle the burgeoning population,
Expert reaction to a paper suggesting that gene drives could be used to help control grey squirrel numbers in the UK
16540Anonymous, Science Media Centre, 2021-03-04 15:59:10.
This study assesses the prospects for using a gene drive to control invasive grey squirrels in the UK. This is a modelling study exploring the potential for such an approach – no such gene drives currently exist and developing them for grey squirrels would be quite a long-term project. Invasive species are a major problem for biodiversity and conservation; in many cases there are no adequate methods for control. Genetic methods may provide new options, potentially both more effective and with fewer off-target effects. Most work on gene drives has focused on mosquitoes; this study is unusual in focusing on a vertebrate (grey squirrel), though there has also been interest in targeting invasive populations of mice and rats on islands.
CRISPR gene drives may come to a squirrel near you.
16536Anonymous, NewsBeezer, 2021-03-04 15:48:43.
Today’s gene drive technologies could be blended to provide control of the invasive gray squirrel population in the UK – with minimal risk to other populations, according to a new modeling published in the journal Scientific reports. Gene driving introduces altered genes into a population that can cause infertility in women. This allows scientists to control the size of the population. However, this tactic faces technical difficulties such as controlling the spread of altered genes while certain animals that are part of the gene drive population mate with uncontrolled populations ̵
Population genomics of invasive rodents on islands: Genetic consequences of colonization and prospects for localized synthetic gene drive
16657K. P. Oh, A. B. Shiels, L. Shiels, D. V. Blondel, K. J. Campbell, J. R. Saah, A. L. Lloyd, P. Q. Thomas, F. Gould, Z. Abdo, J. R. Godwin and A. J. Piaggio, Evolutionary Applications, 2021-02-22 17:41:41.
Here we used pooled whole-genome sequencing of invasive mouse (Mus musculus) populations on four islands along with paired putative source populations to test genetic predictions of island colonization and characterize locally fixed Cas9 genomic targets. Patterns of variation across the genome reflected marked reductions in allelic diversity in island populations and moderate to high degrees of differentiation from nearby source populations despite relatively recent colonization. Locally fixed Cas9 sites in female fertility genes were observed in all island populations, including a small number with multiplexing potential. In practice, rigorous sampling of presumptive LFA will be essential to fully assess risk of resistance alleles. These results should serve to guide development of improved, spatially limited gene drive design in future applications.
Grey squirrels: is birth control the solution to Britain’s invasive species problem?
16275J. Gilchrist, The Conversation, 2021-02-03 17:03:29.
As with the UK’s other invasive species, such as rabbits, signal crayfish and Japanese knotweed, introducing the grey squirrel has proved to be an expensive mistake. Not only do grey squirrels displace red squirrels, they strip bark from trees. A recent report estimated that this could cost commercial forestry and native woodlands £1.1 billion (US$1.5 billion) over the next 40 years, including revenue lost to damaged timber, reduced carbon storage, tree replacement costs and squirrel control. Despite efforts to kill grey squirrels over several decades, their populations remain large and widespread.
The New Yorker Magazine: Gene Drives as a Tool for Saving Nature
16277E. Heber, Island Conservation, 2021-01-03 17:07:04.
In a recent New Yorker Magazine article, entitled “CRISPR and the Splice to Survive,” journalist and best-selling author Elizabeth Kolbert dives into the world of gene drive research. She touches on aspects of gene drive research from altering the toxin produced by cane toads to recovering nearly-extinct trees to eradicating invasive mice through attrition, all to understand the possibilities this tool could hold.
Polyandry blocks gene drive in a wild house mouse population
15390A. Manser, B. Konig and A. K. Lindholm, Nature Communications, 11:8. 2020-12-11 14:12:22.
Here, we study the impact of polyandry on a well-known gene drive, called t haplotype, in an intensively monitored population of wild house mice. First, we show that house mice are highly polyandrous: 47% of 682 litters were sired by more than one male. Second, we find that drive-carrying males are particularly compromised in sperm competition, resulting in reduced reproductive success. As a result, drive frequency decreased during the 4.5 year observation period. Overall, we provide the first direct evidence that the spread of a gene drive is hampered by reproductive behaviour in a natural population.
Modeling CRISPR gene drives for suppression of invasive rodents
15003S. E. Champer, N. Oakes, R. Sharma, P. García-Díaz, J. Champer and P. W. Messer, bioRxiv, 2020.11.05.369942. 2020-11-05 15:27:54.
Here, we develop a high-fidelity model of an island population of invasive rodents that includes three types of suppression gene drive systems. The individual-based model is spatially explicit and allows for overlapping generations and a fluctuating population size. Our model includes variables for drive fitness, efficiency, resistance allele formation rate, as well as a variety of ecological parameters.
Progress Toward Zygotic and Germline Gene Drives in Mice
14852C. Pfitzner, M. A. White, S. G. Piltz, M. Scherer, F. Adikusuma, J. N. Hughes and P. Q. Thomas, The CRISPR Journal, 3:388-397. 2020-10-20 17:17:24.
Here, we investigated the efficiency of CRISPR-Cas9-based gene drives in Mus musculus by constructing "split drive" systems where gRNA expression occurs on a separate chromosome to Cas9, which is under the control of either a zygotic (CAG) or germline (Vasa) promoter.
Why the UK could end up deploying risky gene drives while ignoring natural biological control
14385J. Mathews, GM Watch, 2020-09-14 15:10:57.
First they cloned Dolly the sheep. Now they’re targeting grey squirrels
Generating single-sex litters: development of CRISPR-Cas9 genetic tools to produce all-male offspring
14343C. Douglas, V. Maciulyte, J. Zohren, D. M. Snell, O. A. Ojarikre, P. J. Ellis and J. M. A. Turner, bioRxiv, 2020.09.07.285536. 2020-09-07 18:52:30.
Using the mouse as a model, we developed a synthetic, two-part bicomponent strategy for generating all-male litters.
Novel combination of CRISPR-based gene drives eliminates resistance and localises spread
14172N. R. Faber, G. R. McFarlane, R. C. Gaynor, I. Pocrnic, C. B. A. Whitelaw and G. Gorjanc, bioRxiv, 2020-08-27 14:22:46.
We present HD-ClvR, a novel combination of CRISPR-based gene drives that eliminates resistance and localises spread. As a case study, we model HD-ClvR in the grey squirrel (Sciurus carolinensis), which is an invasive pest in the UK and responsible for both biodiversity and economic losses.
Viewpoint: Is there a scientific basis to ban gene drive technology that can rid us of virus-carrying rodents and mosquitoes?
13845K. Vavitas, Genetic Literacy Project, 2020-08-18 13:51:23.
Gene drives may be invaluable tools to control the spread of parasites, invasive species, and disease carriers. But the technology has faced strong opposition from activist groups and some mainstream scientists based on environmental and food safety. Are these concerns valid?
Towards Responsive Eco-technology: The Development of a Male Sex-biased Mouse
24607W. Kamau, Massachusetts Institute of Technology, 2020-08-16 08:55:45.
CRISPR-Cas systems have catalyzed the emergence of several synthetic population management strategies, like gene drives, for controlling pests and disease vectors. As these technologies garner greater visibility in both general and regulatory audiences, questions have arisen about the invasiveness of drive strategies and have underscored a need for community guidance in designing population management technologies. In heterogametic species, an engineered male-determining chromosome can serve as a method for providing robust and localized population suppression without the need for a gene drive. In mice, X-chromosome inactivation is mediated by X-inactive specific transcript (Xist) long non-coding RNA. I propose to encode a system on the Y chromosome to knock out a necessary region for proper X-inactivation in females. Loss of Xist gene function has no known effects in males or females with a dysfunctional maternal copy, however, females who inherit a dysfunctional paternal copy die at embryonic day 8.5. Thus, this results in a male sex-biased mouse. To create a daughterless mouse, my proof-of-principle design will include a constitutively expressed Cas protein with at minimum a two-guide array. Additionally, I will draw on the ecological species concept found in some cultures, like the M¯aori of New Zealand, to create an alternate eco-cisgenic version using cisgenic murine elements and a CRISPR system found in a commensal species of bacteria. Creating a cisgenic non-driving mammalian model of a genetic population suppression system would be a first-of-its-kind example to show how biological engineering design decisions can be congruent with culturally specific notions of ecology.
Development of zygotic and germline gene drives in mice
12531C. Pfitzner, J. N. Hughes, M. A. White, M. Scherer, S. G. Piltz and P. Q. Thomas, bioRxiv, 2020-06-21 15:15:40.
Here we investigated the efficiency of CRISPR/Cas9-based gene drives in Mus musculus by constructing "split drive" systems with Cas9 under the control of zygotic (CAG) or germline (Vasa) promoters.
What squirrels can teach us about why, when, and how to use gene drives
8184Rebecca Nesbit, synbiobeta, 2020-03-05 20:03:01.
As the last ice age drew to a close, red squirrels made Britain their home. They adapted to a changing landscape and thrived as the UK’s only squirrel species. That all changed in 1876 when grey squirrels were introduced to England from North America as an ornamental species in the grounds of stately homes.
Can CRISPR Save Tufty Fluffytail?
6954L. Tracey, JSTOR Daily, 2020-01-24 16:19:51.
The native red squirrel population in the UK has been decimated by the encroachment of its American cousin, an invasive species. Could a “gene drive” hel
Mosquitoes Genetically Engineered To Resist Dengue Fever
6951R. Bailey, reason, 2020-01-24 16:17:17.
Gene drives could spread this beneficial trait through wild mosquito populations.
DNA ‘edit’ that could wipe out grey invaders
6249Levy, A., Scottish Daily Mail, 2020-01-07 19:25:25.
It is the big, brash invasive species whose advance has left the native red squirrel clinging on for survival in areas where once it thrived. But the march of the grey squirrel could be halted by a 'gene drive', say researchers at the laboratory responsible for Dolly the sheep.
Scenario analysis on the use of rodenticides and sex-biasing gene drives for the removal of invasive house mice on islands
6221M. E. Serr, R. X. Valdez, K. S. Barnhill-Dilling, J. Godwin, T. Kuiken and M. Booker, Biological Invasions, 2020-01-06 21:34:59.
Since the 1960s conservation efforts have focused on recovering island biodiversity by eradicating invasive rodents. These eradication campaigns have led to considerable conservation gains, particularly for nesting seabirds. However, eradications are complex and lengthy endeavors and are even more challenging when humans are co-inhabitants of the targeted island. Furthermore, the method of eradication matters and recent proposals to consider genetic technologies for rodent eradication require specific scrutiny. One such technology is the potential use of a gene drive for biasing offspring sex ratios in invasive house mice, Mus musculus, that would spread and prevent the production of one sex, allowing die-off from lack of reproduction and natural attrition. Practitioners can gain insight into the potential for adoption of this technology from examining stakeholder engagement. This paper uses scenario analysis to address the eradication of rodents on inhabited and uninhabited islands, by specifically comparing the traditional approach of using rodenticides with sex-biasing gene drives. Concurrently the International Union for Conservation of Nature is assessing the risks and value of gene drives in general for conservation. Hence, we make the case that the ethical challenges with the use of gene drive sex-biasing techniques and the effectiveness of this tool will rely as much on its public acceptance and its democratic use as the actual science used to construct the technology.
Red squirrels to thrive again in Britain as new plan considered to eradicate grey breed
6246Hudson, W., Express, 2020-01-06 19:17:19.
RED SQUIRRELS could soon be thriving in Britain again as a new plan to put an end to destructive grey squirrels is being developed. The 150 year reign of the grey squirrel could come to a halt from DNA editing to ensure all future females are born infertile. Researchers at the Roslin Institute want to create gene-edited squirrels for eventual release into the wild. The genetics laboratory is renowned for its 1996 creation of Dolly the Sheep, the world’s first mammal cloned from an adult cell.
Scientists want to hack grey squirrels to death
6243Cutlack, C., Gizmodo, 2020-01-06 19:11:01.
Scottish scientists are planning to hack the DNA of the often-hated grey squirrel, in hope that selectively breeding a broken female strain could lead to their eventual eradication from the wild. It's the only way a map of Scotland is likely to turn red in the foreseeable future.
Scientists behind Dolly the sheep want to edit squirrel DNA to get rid of greys and protect reds UK
6240Bedoya, D., Inforsurhoy, 2020-01-06 19:05:21.
The scientists who cloned Dolly the sheep are now targeting grey squirrels in a bid to rid Britain of them altogether.
First they cloned Dolly the sheep. Now they’re targeting grey squirrels
6218Leake, J., The Times, 2020-01-05 21:25:05.
For 150 years they have wreaked havoc on Britain’s woods and wildlife, but the destructive reign of the grey squirrel could soon be over — ended by DNA editing to ensure that all future females are born infertile. Researchers at the Roslin Institute, the genetics laboratory renowned for its 1996 creation of Dolly the Sheep, the world’s first mammal cloned from an adult cell, want to create gene-edited squirrels for eventual release into the wild.
Dolly the sheep scientists hope DNA editing can wipe out grey squirrels
6215McLaughlin, M., The Scotsman, 2020-01-05 21:20:21.
They have been poisoned, shot at, and stumbled into traps laid by those who regard them as a ruinous blight on the country’s woodland and wildlife. But now, the grey squirrel is facing arguably its biggest threat yet, with plans to harness the cutting edge of genetic science to bring their destructive reign to an end.
A selfish genetic element linked to increased lifespan impacts metabolism in female house mice
5652Lopes, P. C. and A. K. Lindholm, The Journal of Experimental Biology, 2019:212704. 2019-12-17 18:01:15.
Gene drive systems can lead to the evolution of traits that further enhance the transmission of the driving element. In gene drive, one allele is transmitted to offspring at a higher frequency than the homologous allele. This has a range of consequences, which generally include a reduction in fitness of the carrier of the driving allele, making such systems “selfish”. The t haplotype is one such driver, found in house mice. It is linked to a reduction in litter size in matings among heterozygous animals, but also to increased lifespan in wild females that carry it. Here, we tested whether carrying the t haplotype was associated with altered resting metabolic rate (RMR). We show that females carrying the t haplotype decrease RMR as they increase in size, compared to wildtype females or males of either genotype. Our study elucidates a plausible mechanism by which a selfish genetic element increases lifespan.
Genetically engineering wild mice to combat Lyme disease: An ecological perspective
5631Snow, A. A., BioScience, 69:746-756. 2019-12-17 16:51:55.
Genetic engineering of wild populations has been proposed for reducing human diseases by altering pathogens’ hosts. For example, CRISPR- based genome editing may be used to create white-footed mice (Peromyscus leucopus) that are resistant to the Lyme disease spirochete vectored by blacklegged ticks (Ixodes scapularis). Toward this goal, academic researchers are developing Lyme-resistant and tick-resistant white-footed mice, which are a primary pathogen reservoir for Lyme disease in the United States. If field trials on small, experimental islands are successful, the project would scale up to the larger islands of Nantucket and Martha’s Vineyard, Massachusetts, and possibly to the mainland, most likely with a local gene drive to speed the traits’ proliferation, pending approvals from relevant constituents. Despite considerable publicity, this project has yet to be evaluated by independent professional ecologists. In the present article, I discuss key ecological and evolutionary questions that should be considered before such genetically engineered mice are released into natural habitats
Effects of a male meiotic driver on male and female transcriptomes in the house mouse
6639A. Lindholm, A. Sutter, S. Kunzel, D. Tautz and H. Rehrauer, Proceedings of the Royal Society B-Biological Sciences, 286:1-8. 2019-11-13 20:18:05.
Not all genetic loci follow Mendel's rules, and the evolutionary consequences of this are not yet fully known. Genomic conflict involving multiple loci is a likely outcome, as restoration of Mendelian inheritance patterns will be selected for, and sexual conflict may also arise when sexes are differentially affected. Here, we investigate effects of the t haplotype, an autosomal male meiotic driver in house mice, on genome-wide gene expression patterns in males and females. We analysed gonads, liver and brain in adult same-sex sibling pairs differing in genotype, allowing us to identify t-associated differences in gene regulation. In testes, only 40% of differentially expressed genes mapped to the approximately 708 annotated genes comprising the t haplotype. Thus, much of the activity of the t haplotype occurs in trans, and as upregulation. Sperm maturation functions were enriched among both cis and trans acting t haplotype genes. Within the t haplotype, we observed more downregulation and differential exon usage. In ovaries, liver and brain, the majority of expression differences mapped to the t haplotype, and were largely independent of the differences seen in the testis. Overall, we found widespread transcriptional effects of this male meiotic driver in the house mouse genome.
Rodent gene drives for conservation: opportunities and data needs
6386J. Godwin, M. Serr, K. Barnhill-Dilling, D. V. Blondel, P. R. Brown, K. Campbell, J. Delborne, A. L. Lloyd, K. P. Oh, T. A. A. Prowse, R. Saah and P. Thomas, Proceedings of the Royal Society B-Biological Sciences, 286:20191606. 2019-11-10 16:22:06.
Invasive rodents impact biodiversity, human health and food security worldwide. The biodiversity impacts are particularly significant on islands, which are the primary sites of vertebrate extinctions and where we are reaching the limits of current control technologies. Gene drives may represent an effective approach to this challenge, but knowledge gaps remain in a number of areas. This paper is focused on what is currently known about natural and developing synthetic gene drive systems in mice, some key areas where key knowledge gaps exist, findings in a variety of disciplines relevant to those gaps and a brief consideration of how engagement at the regulatory, stakeholder and community levels can accompany and contribute to this effort. Our primary species focus is the house mouse, Mus musculus, as a genetic model system that is also an important invasive pest. Our primary application focus is the development of gene drive systems intended to reduce reproduction and potentially eliminate invasive rodents from islands. Gene drive technologies in rodents have the potential to produce significant benefits for biodiversity conservation, human health and food security. A broad-based, multidisciplinary approach is necessary to assess this potential in a transparent, effective and responsible manner.
Gene Drive and Thinking Animals
5541Island Conservation, 2019-11-04 20:54:55.
Royden Saah, Island Conservation's GBIRd program manager, recently spoke at the Thinking Animals Summit alongside Leilani Münter, a former professional race car driver and environmental activist. The Genetic Biocontrol of Invasive Rodents partnership (GBIRd) is designed for exactly that purpose. The partnership is made up of governments, NGOs, and research universities that are dedicated to understanding if the use of gene drives in mice can effectively eradicate invasive rodents on islands as well as the social implications of this science.
Self-destructing mosquitoes and sterilized rodents: the promise of gene drives
6645M. Scudellari, Nature, 571:160-162. 2019-07-09 20:27:18.
Altering the genomes of entire animal populations could help to defeat disease and control pests, but researchers worry about the consequences of unleashing this new technology.
Exploring Stakeholder Perspectives on the Development of a Gene Drive Mouse for Biodiversity Protection on Islands: Workshop Report
11581M. Farooque, S. K. Barnhill-Dilling, J. Shapiro and J. Delborne, North Carolina State University, 2019-06-01 15:28:38.
The “Exploring Stakeholder Perspectives on the Development of a Gene Drive Mouse for Biodiversity Protection” workshop was held on the North Carolina State University campus in Raleigh, NC on March 7-8, 2019, aiming to convene a diverse group of stakeholders, scientists, funders, and leaders for an exploration of perspectives on the development of a gene drive mouse for restoring biodiversity on islands. Information collected at the workshop is presented in this report to inform upcoming decisions by the NCSU-Safe Genes research team about research, testing, and potential deployment of technologies (the Safe Genes program does not fund any environmental releases of gene drive modified organisms), as well as future engagement activities.
Genetic pest management technologies to control invasive rodents
11576D. Kanavy and D. Threadgill, Island invasives: scaling up to meet the challenge, 2019-03-05 15:20:05.
Many strategies exist to manage invasive pests on islands, ranging from poison to trapping, with varying degrees of success. Genetic technologies are increasingly being applied to insect pests, but so far, not to vertebrates. We are implementing a genetic strategy to eradicate invasive mouse populations as another tool for pest control. Mus musculus, the common house mouse, is one of the most widespread invasive species. Mice threaten human health, agriculture, and biodiversity on many islands, particularly seabirds. Seabirds are endangered indirectly through competition for resources or predators being attracted by the mice or directly with mice attacking chicks and eggs. Rodenticides are the most common method of eradicating mice, but their use leads to poisoning of non-target species and has limited efficacy against mice. An approach that could eliminate non-target species impact would be to engineer daughterless mice linked to a gene drive system for self-sustained propagation. For this project, we have investigated exploiting a naturally occurring gene drive, the t-complex. Using the t w2 haplotype of the t-complex, we observed the t w2 haplotype being transmitted to offspring with a transmission distortion ratio of 95.3%. The daughterless phenotype is being accomplished by inserting the Sry gene (male sex-determining gene) into an autosome containing the tw2 haplotype via CRISPR/Cas9 gene editing. The presence of Sry will induce testis formation, regardless of the sex chromosomes naturally inherited. When Sry is inserted into the t-complex, the desired gene will spread through the population, eliminating female offspring. This model system will support studies to evaluate the effectiveness of crashing an invasive population without adversely affecting other
Trialling gene drives to control invasive species: what, where and how?
11573T. Harvey-Samuel, K. J. Campbell, M. Edgington and L. Alphey, Island invasives: scaling up to meet the challenge, 2019-03-05 15:16:48.
The control of invasive species would be enhanced through the addition of novel, more effective and sustainable pest management methods. One control option yet to be trialled in the field is to deploy transgene-based ‘Gene Drives’: technologies which force the inheritance of a genetic construct through the gene pool of a wild population, suppressing it or replacing it with a less harmful form. There is considerable interest in applying gene drives to currently intractable invasives across a broad taxonomic range. However, not all species will make efficient or safe targets for these technologies. Additionally, the safety and efficacy of these systems will vary according to where they are deployed, the specific molecular design chosen, and how these factors interact with the ecology of the target pest. Given the transformative but also controversial nature of gene drives, it is imperative that their first field trials are able to successfully demonstrate that they can be used safely and efficiently. Here, we discuss how to maximise the probability of this outcome through considering three important questions: What types of invasive species should we use to trial gene drives? Where should we be trialling them? and How should these trials be conducted? In particular, we focus on the ecological, genetic and geographic features of small, isolated islands which make them ideal locations for these initial trials. A case study of an island invasive that is deemed highly appropriate for gene drive intervention, and for which gene drive development is currently underway (Mus musculus), is used to further explore these concepts
Towards a genetic approach to invasive rodent eradications: assessing reproductive competitiveness between wild and laboratory mice
11570M. Serr, N. Heard and J. Godwin, Island invasives: scaling up to meet the challenge, 2019-03-05 15:10:12.
House mice are significant invasive pests, particularly on islands without native mammalian predators. As part of a multi-institutional project aimed at suppressing invasive mouse populations on islands, we aim to create heavily male-biased sex ratios with the goal of causing the populations to crash. Effective implementation of this approach will depend on engineered F1 wild-lab males being effective secondary invaders that can mate successfully. As a first step in assessing this possibility, we are characterising genetic and behavioural differences between Mus musculus strains in terms of mating and fecundity using wild house mice derived from an invasive population on the Farallon Islands (MmF), a laboratory strain C57BL/6/129 (tw2), and F1 wild-lab off spring. Mice with the ‘t allele’ (tw2) have a naturally occurring gene drive system. To assess fertility in F1 wild-lab crosses, tw2 males were paired with wild-derived females from the Farallon Islands (MmF). Results of these matings indicate litter sizes are comparable but that weaned pup and adult wild-lab mice are heavier in mass. Next, we initiated tests of male competitiveness using larger (3 m2 ) enclosures with enrichment. We introduced both an MmF and a tw2-bearing male to two MmF females to assess mating outcomes. Preliminary results of these experiments show none of the offspring carried the t-allele. However, performing the same experiment with F1 wildlab males instead of a full lab background resulted in 70% of off spring carrying the t w2 allele. This indicates that F1 wildlab males may be able to successfully compete and secondarily invade. It will be important in subsequent experiments to determine what characteristics contribute to secondary invasion success. More generally, a better understanding of characteristics contributing to overall success in increasingly complex and naturalistic environments will be critical in determining the potential of a gene drive-based eradication approach for invasive mice on islands
A potential new tool for the toolbox: assessing gene drives for eradicating invasive rodent populations
11550K. J. Campbell, J. R. Saah, P. R. Brown, J. Godwin, F. Gould, G. R. Howald, A. Piaggio, P. Thomas, D. M. Tompkins, D. Threadgill, J. Delborne, D. Kanavy, T. Kuiken, H. Packard, M. Serr and A. Shiels, Island invasives: scaling up to meet the challenge, 2019-03-05 14:59:34.
Invasive rodents have significant negative impacts on island biodiversity. All but the smallest of rodent eradications currently rely on island-wide rodenticide applications. Although signifi cant advances have been made in mitigating unintended impacts, rodent eradication on inhabited islands remains extremely challenging. Current tools restrict eradication eff orts to fewer than 15% of islands with critically endangered or endangered species threatened by invasive rodents. The Genetic Biocontrol of Invasive Rodents partnership is an interdisciplinary collaboration to develop and evaluate gene drive technology for eradicating invasive rodent populations on islands. Technological approaches currently being investigated include the production of multiple strains of Mus musculus with a modifi ed form of the native t-complex, or a CRISPR gene drive, carrying genes or mechanisms that determine sex. These systems have the potential to skew the sex ratio of off spring to approach 100% single-sex, which could result in population collapse. One goal proposed is to test the ability of constructs to spread and increase in frequency in M. musculus populations in biosecure, captive settings and undertake modelling to inform development and potential deployment of these systems. Structured ecologically-based risk assessments are proposed, along with social and cultural engagement to assess the acceptability of releasing a gene drive system. Work will be guided by an external ethics advisory board. Partners are from three countries with significant regulatory capacity (USA, Australia, New Zealand). Thus, we will seek data sharing agreements so that results from experiments may be used within all three countries and treat regulatory requirements as a minimum. Species-specific, scalable, and socially acceptable new eradication tools could produce substantial biodiversity benefits not possible with current technologies. Gene drive innovation may provide such a tool for invasive species management and be potentially transformative and worthy of exploring in an inclusive, responsible, and ethical manner.
Gene drive technology makes mouse offspring inherit specific traits from parents
4531Cooper, KLG, Hannah A., The Conversation, 2019-01-24 00:00:00.
As mouse geneticists, we spend a lot of time waiting for mice to make more mice. Their small size, ease of care and willingness to mate have made mice the “mammal of choice” for scientists for more than a century. Indeed, these wriggly fur balls that strike fear in the hearts of some are owed a debt of gratitude for all they’ve taught researchers about human health and how mammalian bodies are built and function.
Gene drive tested in mice – Expert Reaction
4541Science Media Centre, Science Media Centre, 2019-01-24 00:00:00.
Using CRISPR genome editing, the researchers developed a process to make a gene more likely to be inherited than by chance alone. Their attempts with male mice were unsuccessful, but when it was used in females they increased the inheritance of the desired gene from 50 per cent to about 70 per cent, which they say might be enough for use in the lab.
Gene editing research highlights challenges in using CRISPR for pest control
4532Dreaver, C, Radio New Zealand, 2019-01-24 00:00:00.
US researchers have had some success in using the gene editing technique CRISPR to test out a gene drive in mice, to modify their genes - highlighting the challenges researchers face if it were to be used in pest eradication.
Gene drive, a powerful way to speed genetic inheritance, shown for first time in mammals, UCSD researchers say
4533Fikes, BJ, San Diego Union Tribune, 2019-01-23 00:00:00.
Gene drive -- the ability to shortcut genetic inheritance by propelling a gene throughout a population -- has been demonstrated in principle for the first time in mammals.; ; UC San Diego scientists reported this feat in mice in a study released Wednesday in the journal Nature. It can be found at http://j.mp/ucsdgenedrive. A previous study from UCSD researchers demonstrated this feat in insects, also a first at its time
Gene Drives Work in Mice (if They’re Female)
4538Rennie, JC, Jordana, Quanta Magazine, 2019-01-23 00:00:00.
Conservationists and bioethicists often regard the packages of engineered DNA called “gene drives” with a mixture of wonder, excitement and dread. Gene drives violate the normal rules of inheritance by making sure they get passed down to all of their host organism’s offspring, not just to half of them; they therefore have the unnerving potential to rapidly and irrevocably alter a population. Much of the controversy about gene drives has centered on the practicality (and hubris) of using them to control dangerous insect pests, since insects were about the only animals in which gene drives had been shown to work.
La reacción genética en cadena llega a los mamíferos
4537Mediavilla, D, El Pais, 2019-01-23 00:00:00.
Un experimento muestra que la edición de los genes puede introducir cambios en especies completas que permitan incluso su extinción en un área geográfica
Researchers first to use CRISPR/Cas9 to control genetic inheritance in mice
4529University of California, Phys Org, 2019-01-23 00:00:00.
Biologists at the University of California San Diego have developed the world's first CRISPR/Cas9-based approach to control genetic inheritance in a mammal.
Scientists rewrite mice DNA so genes can be spread through species
4539Sample, I, The Guardian, 2019-01-23 00:00:00.
Controversial procedure has huge potential to combat diseases such as malaria
US scientists overturn genetic inheritance rules in lab mice
4530Cookson, C, Financial Times, 2019-01-23 00:00:00.
New gene drive technology that could revolutionise biology research has been demonstrated for the first time in mammals, after US scientists overturned the normal rules of genetic inheritance in laboratory mice.; ; Scientists at the University of California San Diego employed the technology to turn a group of lab mice white, using a complex DNA editing procedure that allowed a white-coat mutation to spread through successive generations of animals with unnatural speed.
On the road to a gene drive in mammals
3902Conklin, BR, Nature, 566:43-45. 2019-01-20 00:00:00.
A method for making a version of a gene more likely to be inherited than normal, generating what is called a gene drive, might be used to control insect populations. It has now been reported to work in mammals, too.
A Y-chromosome shredding gene drive for controlling pest vertebrate populations
3938Prowse, TAAA, F.; Cassey, P.; Thomas, P.; Ross, J. V., eLife, 8:19. 2019-01-16 00:00:00.
Self-replicating gene drives that modify sex ratios or infer a fitness cost could be used to control populations of invasive alien species. The targeted deletion of Y sex chromosomes using CRISPR technology offers a new approach for sex bias that could be incorporated within gene-drive designs. We introduce a novel gene-drive strategy termed Y-CHromosome deletion using Orthogonal Programmable Endonucleases (Y-CHOPE), incorporating a programmable endonuclease that 'shreds' the Y chromosome, thereby converting XY males into fertile XO females. Firstly, we demonstrate that the CRISPR/Cas12a system can eliminate the Y chromosome in embryonic stem cells with high efficiency (c. 90%). Next, using stochastic, individual-based models of a pest mouse population, we show that a Y-shredding drive that progressively depletes the pool of XY males could effect population eradication through mate limitation. Our molecular and modeling data suggest that a Y-CHOPE gene drive could be a viable tool for vertebrate pest control.
Super-Mendelian inheritance mediated by CRISPR-Cas9 in the female mouse germline
3914Grunwald, HAG, V. M.; Poplawski, G.; Xu, X. R. S.; Bier, E.; Cooper, K. L., Nature, 566:105-109. 2019-01-12 00:00:00.
A gene drive biases the transmission of one of the two copies of a gene such that it is inherited more frequently than by random segregation. Highly efficient gene drive systems have recently been developed in insects, which leverage the sequence-targeted DNA cleavage activity of CRISPR-Cas9 and endogenous homology-directed repair mechanisms to convert heterozygous genotypes to homozygosity(1-4). If implemented in laboratory rodents, similar systems would enable the rapid assembly of currently impractical genotypes that involve multiple homozygous genes (for example, to model multigenic human diseases). To our knowledge, however, such a system has not yet been demonstrated in mammals. Here we use an active genetic element that encodes a guide RNA, which is embedded in the mouse tyrosinase (Tyr) gene, to evaluate whether targeted gene conversion can occur when CRISPR-Cas9 is active in the early embryo or in the developing germline. Although Cas9 efficiently induces double-stranded DNA breaks in the early embryo and male germline, these breaks are not corrected by homology-directed repair. By contrast, Cas9 expression limited to the female germline induces double-stranded breaks that are corrected by homology-directed repair, which copies the active genetic element from the donor to the receiver chromosome and increases its rate of inheritance in the next generation. These results demonstrate the feasibility of CRISPR-Cas9-mediated systems that bias inheritance of desired alleles in mice and that have the potential to transform the use of rodent models in basic and biomedical research.
A genetic system for biasing the sex ratio in mice
3952Yosef, IEB, Liat; Globus, Rea; Shlomovitz, Inbar; Munitz, Ariel; Gerlic, Motti; Qimron, Udi, EMBO reports, 20:e48269. 2019-01-10 00:00:00.
Biasing the sex ratio of populations of different organisms, including plants, insects, crustacean, and fish, has been demonstrated by genetic and non-genetic approaches. However, biasing the sex ratio of mammalian populations has not been demonstrated genetically. Here, we provide a first proof of concept for such a genetic system in mammals by crossing two genetically engineered mouse lines. The maternal line encodes a functional Cas9 protein on an autosomal chromosome, whereas the paternal line encodes guide RNAs on the Y chromosome targeting vital mouse genes. After fertilization, the presence of both the Y-encoded guide RNAs from the paternal sperm and the Cas9 protein from the maternal egg targets the vital genes in males. We show that these genes are specifically targeted in males and that this breeding consequently self-destructs solely males. Our results pave the way for a genetic system that allows biased sex production of livestock.
Locally Fixed Alleles: A method to localize gene drive to island populations
3948Sudweeks, JH, Brandon; Blondel, Dimitri V.; Campbell, Karl J.; Dhole, Sumit; Eisemann, John D.; Edwards, Owain; Godwin, John; Howald, Gregg R.; Oh, Kevin P.; Piaggio, Antoinette J.; Prowse, Thomas A. A.; Ross, Joshua V.; Saah, J. Royden; Shiels, Aaron B.; Thomas, Paul Q.; Threadgill, David W.; Vella, Michael R.; Gould, Fred; Lloyd, Alun L., Scientific Reports, 9:15821. 2019-01-06 00:00:00.
Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach, but the potential for drive-bearing individuals to escape from the target release area and impact populations elsewhere is a major concern. Here we propose the “Locally Fixed Alleles” approach as a novel means for localizing elimination by a drive to an island population that exhibits significant genetic isolation from neighboring populations. Our approach is based on the assumption that in small island populations of rodents, genetic drift will lead to alleles at multiple genomic loci becoming fixed. In contrast, multiple alleles are likely to be maintained in larger populations on mainlands. Utilizing the high degree of genetic specificity achievable using homing drives, for example based on the CRISPR/Cas9 system, our approach aims at employing one or more locally fixed alleles as the target for a gene drive on a particular island. Using mathematical modeling, we explore the feasibility of this approach and the degree of localization that can be achieved. We show that across a wide range of parameter values, escape of the drive to a neighboring population in which the target allele is not fixed will at most lead to modest transient suppression of the non-target population. While the main focus of this paper is on elimination of a rodent pest from an island, we also discuss the utility of the locally fixed allele approach for the goals of population suppression or population replacement. Our analysis also provides a threshold condition for the ability of a gene drive to invade a partially resistant population.
Controlling invasive rodents via synthetic gene drive and the role of polyandry
3927Manser, AC, S. J.; Sutter, A.; Blondel, D. V.; Serr, M.; Godwin, J.; Price, T. A. R., Proceedings of the Royal Society B-Biological Sciences, 286:9. 2019-01-05 00:00:00.
House mice are a major ecosystem pest, particularly threatening island ecosystems as a non-native invasive species. Rapid advances in synthetic biology offer new avenues to control pest species for biodiversity conservation. Recently, a synthetic sperm-killing gene drive construct called t-Sry has been proposed as a means to eradicate target mouse populations owing to a lack of females. A factor that has received little attention in the discussion surrounding such drive applications is polyandry. Previous research has demonstrated that sperm-killing drivers are extremely damaging to a male's sperm competitive ability. Here, we examine the importance of this effect on the t-Sry system using a theoretical model. We find that polyandry substantially hampers the spread of t-Sry such that release efforts have to be increased three-to sixfold for successful eradication. We discuss the implications of our finding for potential pest control programmes, the risk of drive spread beyond the target population, and the emergence of drive resistance. Our work highlights that a solid understanding of the forces that determine drive dynamics in a natural setting is key for successful drive application, and that exploring the natural diversity of gene drives may inform effective gene drive design.
Genetic manipulation of sex ratio in mammals: the Reaper comes for Mickey
3947Smanski, MJZ, David, EMBO reports, 20:e48577. 2019-01-05 00:00:00.
In most animals, sexual reproduction results in a 1:1 ratio of females to males. For several sectors of agriculture, for example, milk or egg production, only a single sex is needed. Biasing the sex ratio so that only offspring of the desired sex are produced has the potential to increase breeding efficiency. In this issue of EMBO Reports, Yosef et al [1] demonstrate a genetic approach to bias the sex ratio in mice by specifically disrupting essential genes in male embryos. Their approach is an important first step toward generating sex-ratio biasing applications for agriculture
Sustainability as a framework for considering gene drive mice for invasive rodent eradication
3886Barnhill-Dilling, SKS, M.; Blondel, D. V.; Godwin, J., Sustainability, 11:1334. 2019-01-04 00:00:00.
Gene drives represent a dynamic and controversial set of technologies with applications that range from mosquito control to the conservation of biological diversity on islands. Currently, gene drives are being developed in mice that may one day serve as an important tool for reducing invasive rodent pests, a key threat to island biodiversity and economies. Gene drives in mice are still in development in laboratories, and wild release of modified mice is likely a distant reality. However, technological changes outpace the existing capacity of regulatory frameworks, and thus require integrated governance frameworks. We suggest sustainability-which gives equal consideration to the environment, economy, and society-as one framework for addressing complexity and uncertainty in the governance of emerging gene drive technologies for invasive species management. We explore the impacts of rodent gene drives on island environments, including potential conservation and restoration of island biodiversity. We outline considerations for rodent gene drives on island economies, including impacts on agricultural and tourism losses, and reductions in biosecurity costs. Finally, we address the social dimension as an essential space for deliberation that will be integral to evaluating the potential deployment of gene drive rodents on islands.
CRISPR Gene Drive (Complete guide 2019)
5507Every Cell A Universe, 2018-11-18 18:59:09.
Crispr gene drive - malaria cure and a new way to look at conservation.
Gene Drive
4551Collins, CH, Scientific American, 2018-09-14 00:00:00.
Research into a genetic engineering technology that can permanently change the traits of a population or even an entire species is progressing rapidly. The approach uses gene drives—genetic elements that pass from parents to unusually high numbers of their offspring, thereby spreading through populations rather quickly. Gene drives occur naturally but can also be engineered, and doing so could be a boon to humanity in many ways. The technology has the potential to stop insects from transmitting malaria and other terrible infections, enhance crop yields by altering pests that attack plants, render corals resistant to environmental stress, and keep invasive plants and animals from destroying ecosystems. Yet investigators are deeply aware that altering or even eliminating a species could have profound consequences. In response, they are developing rules to govern the transfer of gene drives from the laboratory into future field tests and wider use.
Developing gene drive technologies to eradicate invasive rodents from islands
13798C. M. Leitschuh, D. Kanavy, G. A. Backus, R. X. Valdez, M. Serr, E. A. Pitts, D. Threadgill and J. Godwin, Journal of Responsible Innovation, 5:S121-S138. 2018-01-24 15:45:57.
Gene drive methods of rodent eradication offer an alternative to killing that has the potential to be more species-specific, more humane, and more biologically safe for use around humans. Implementing this technology would involve releasing laboratory-developed engineered mice into wild populations. Some areas for further research include assessing the ecological effects of releasing engineered mice, the potential risks for the accidental or deliberate release of genetically modified organisms into mainland mouse populations, and the social, ethical, and regulatory acceptability of the technology.
Carrying a selfish genetic element predicts increased migration propensity in free-living wild house mice
4012Runge, J-NL, Anna K., Proceedings of the Royal Society B: Biological Sciences, 285:20181333. 2018-01-10 00:00:00.
Life is built on cooperation between genes, which makes it vulnerable to parasitism. Selfish genetic elements that exploit this cooperation can achieve large fitness gains by increasing their transmission relative to the rest of the genome. This leads to counter-adaptations that generate unique selection pressures on the selfish genetic element. This arms race is similar to host–parasite coevolution, as some multi-host parasites alter the host’s behaviour to increase the chance of transmission to the next host. Here, we ask if, similarly to these parasites, a selfish genetic element in house mice, the t haplotype, also manipulates host behaviour, specifically the host’s migration propensity. Variants of the t that manipulate migration propensity could increase in fitness in a meta-population. We show that juvenile mice carrying the t haplotype were more likely to emigrate from and were more often found as migrants within a long-term free-living house mouse population. This result may have applied relevance as the t has been proposed as a basis for artificial gene drive systems for use in population control.
Rats join mosquitoes as targets for ‘gene drive’ pest control.
4596Hirschler, B, Reuters, 2017-12-17 00:00:00.
Rodents have joined mosquitoes in the cross-hairs of scientists working on a next-generation genetic technology known as “gene drive” to control pests.; Researchers in Scotland said on Tuesday they had developed two different ways to disrupt female fertility in rats and mice, building on a similar approach that has already been tested in the lab to eliminate malaria-carrying mosquitoes.; So-called gene drives push engineered genes through multiple generations by over-riding normal biological processes, so that all offspring carry two copies. Usually, animals would receive one copy of a gene from the mother and one from the father.
Open, Local, and Obligated
5467Yale University, 2017-12-13 17:04:29.
Kevin Esvelt, PhD, assistant professor at the MIT Media Lab and leader of the Sculpting Evolution Group talks about the need for new scientific structures based on transparency and open. This lecture was given at the 2017 Editing Nature Summit.
How selfish DNA hijacks its way into egg cells
13516Science, 2017-11-06 13:52:33.
This video was produced by Science magazine and explains and illustrates how gonotaxis or the asymmetrical allocation of chromosomes to developing female gametes occurs in mice. This video reflects an understanding of this process based on the publication by Akera et al (2017).
Spindle asymmetry drives non-Mendelian chromosome segregation
13518T. Akera, L. Chmátal, E. Trimm, K. Yang, C. Aonbangkhen, D. M. Chenoweth, C. Janke, R. M. Schultz and M. A. Lampson, Science, 358:668. 2017-11-03 14:19:19.
Genetic elements compete for transmission through meiosis, when haploid gametes are created from a diploid parent. Selfish elements can enhance their transmission through a process known as meiotic drive. In female meiosis, selfish elements drive by preferentially attaching to the egg side of the spindle. This implies some asymmetry between the two sides of the spindle, but the molecular mechanisms underlying spindle asymmetry are unknown. Here we found that CDC42 signaling from the cell cortex regulated microtubule tyrosination to induce spindle asymmetry and that non-Mendelian segregation depended on this asymmetry. Cortical CDC42 depends on polarization directed by chromosomes, which are positioned near the cortex to allow the asymmetric cell division. Thus, selfish meiotic drivers exploit the asymmetry inherent in female meiosis to bias their transmission.
Could genetic engineering save the Galapagos?
14868S. S. Hall, Scientific American, 2017-11-01 19:26:09.
Campbell has been working on eradications in the Galápagos since 1997, including a 2006 campaign to remove all the feral goats and donkeys from Floreana. A decade later he’s a project manager with Island Conservation, and the most ambitious project on its agenda is once again on Floreana: to eradicate every single rat and mouse on the island.
How Genetically Modified Mice Could One Day Save Island Birds
4593Borel, B, Audubon, 2017-06-07 00:00:00.
The silent black-and-white footage opens on a seemingly tranquil setting: a burrow where an Atlantic Petrel tends to its chick. Then mice begin scurrying in and out of frame. The dark blurs jostle the adult, darting up to the exposed chick and tearing off bloody bites. They’re eating it alive.; ; The horrific scene is captured by nest cams on Gough (rhymes with “off”), a rugged volcanic island about 1,700 miles west of South Africa. It has one of the world’s largest seabird nesting colonies, with millions of birds representing 22 species. It’s also home to hundreds of thousands of mice, descendants of stowaways on 19th-century seal-hunting ships. The tiny predators devour some 900,000 chicks a year and threaten to decimate the island’s Atlantic Petrels and Tristan Albatrosses, which breed here almost exclusively. In a rodent-free landscape, more than two-thirds of the albatross chicks should make it to adulthood; on Gough, mice cut survival to as low as 10 percent.
Sperm competition suppresses gene drive among experimentally evolving populations of house mice
4056Manser, AL, A. K.; Simmons, L. W.; Firman, R. C., Molecular Ecology, 26:5784-5792. 2017-01-14 00:00:00.
Drive genes are genetic elements that manipulate the 50% ratio of Mendelian inheritance in their own favour, allowing them to rapidly propagate through populations. The action of drive genes is often hidden, making detection and identification inherently difficult. Yet drive genes can have profound evolutionary consequences for the populations that harbour them: most known drivers are detrimental to organismal gamete development, reproduction and survival. In this study, we identified the presence of a well-known drive gene called t haplotype post hoc in eight replicate selection lines of house mice that had been evolving under enforced monandry or polyandry for 20 generations. Previous work on these selection lines reported an increase in sperm competitive ability in males evolving under polyandry. Here, we show that this evolutionary response can be partly attributed to gene drive. We demonstrate that drive-carrying males are substantially compromised in their sperm competitive ability. As a consequence, we found that t frequencies declined significantly in the polyandrous lines while remaining at stable, high levels in the monandrous lines. For the first time in a vertebrate, we thus provide direct experimental evidence that the mating system of a species can have important repercussions on the spread of drive genes over evolutionary relevant timescales. Moreover, our work highlights how the covert action of drive genes can have major, potentially unintended impact on our study systems.
Re-Coding for Conservation
4603Hawkes, A, Bay Nature Magazine, 2016-06-27 00:00:00.
very year, as summer turns to fall, the mouse population on the South Farallon Islands explodes to plague-like densities, numbering 490 mice per acre, among the highest found on any island in the world. The scientists who live and work there describe the assault of the invasive house mouse as a kind of purgatory in the otherwise stunning, windswept smattering of rocky islets and sea stacks 30 miles outside the Golden Gate. “At night they would be everywhere,” says Peter Pyle, a wildlife biologist who spent more than 20 fall seasons living at the research station on Southeast Farallon Island. “I had them crawling on top of me at night and in my hair. I tried to mouse-proof the house but we’d catch 50 mice in the night.”
No evidence for female discrimination against male house mice carrying a selfish genetic element
4103Sutter, AL, A. K., Current Zoology, 62:675-685. 2016-01-21 00:00:00.
Meiotic drivers distort transmission to the next generation in their favor, with detrimental effects on the fitness of their homologues and the rest of the genome. Male carriers of meiotic drivers commonly inflict costs on their mates through genetic incompatibility, reduced fecundity, or biased brood sex ratios. Given these costs, evidence for female discrimination against male carriers is surprisingly rare. One of few examples is the t haplotype in house mice, a meiotic driver that shows strong transmission distortion in males and is typically homozygote lethal. As a consequence, mating between 2 t heterozygous (+/t) mice leads to high embryo mortality. Previous experiments showing that +/t females avoid this incompatibility cost by preferring +/+versus +/t males have inferred preference based on olfactory cues or brief social interactions. Evidence from mating contexts in laboratory settings and semi-natural populations has been inconclusive. Here, we investigated female choice from a large number of no-choice mating trials. We found no evidence for discrimination against +/t males based on mating, remating, and copulatory behavior. Further, we found no evidence for avoidance of incompatibility through selective interactions between gametes. The likelihood of mating showed significant effects of female weight and genotype, suggesting that our test paradigm enabled females to exhibit mate choice. We discuss the strengths and limitations of our approach. By explicitly considering selection at both the individual and gene level, we argue why precopulatory female discrimination by +/t females may be less evolutionarily stable than discrimination by all females based on postcopulatory mechanisms.
Meiotic drive changes sperm precedence patterns in house mice: potential for male alternative mating tactics?
4104Sutter, AL, A. K., BMC Evolutionary Biology, 16:15. 2016-01-02 00:00:00.
Background: With female multiple mating (polyandry), male-male competition extends to after copulation (sperm competition). Males respond to this selective pressure through physiological, morphological and behavioural adaptations. Sperm competitiveness is commonly decreased in heterozygote carriers of male meiotic drivers, selfish genetic elements that manipulate the production of gametes in males. This might give carriers an evolutionary incentive to reduce the risk of sperm competition. Here, we explore this possibility in house mice. Natural populations frequently harbour a well-characterised male driver (t haplotype), which is transmitted to 90 % of heterozygous (+/t) males' offspring. Previous research demonstrated strong detrimental effects on sperm competitiveness, and suggested that +/t males are particularly disadvantaged against wild type males when first-to-mate. Low paternity success in the first-to-mate role is expected to favour male adaptations that decrease the risk of sperm competition by preventing female remating. Genotype-specific paternity patterns (sperm precedence) could lead to genetically determined alternative reproductive tactics that can spread through gene level selection. Here, we seek confirmation that +/t males are generally disadvantaged when first-to-mate and address whether males of different genotypes differ in reproductive tactics (copulatory and morphological) to maximise individual or driver fitness. Finally, we attempt to explain the mechanistic basis for alternative sperm precedence patterns in this species. Results: We confirmed that +/t males are weak sperm competitors when first to mate. When two +/t males competed, the second-to-mate was more successful, which contrasts with first male sperm precedence when wild type males competed. However, we found no differences between male genotypes in reproductive behaviour or morphology that were consistent with alternative reproductive tactics. Sperm of +/+ and +/t males differed with respect to in vitro sperm features. Premature hypermotility in +/t males' sperm can potentially explain why +/t males are very weak sperm competitors when first-to-mate. Conclusions: Our results demonstrate that meiotic drivers can have strong effects on sperm precedence patterns, and may provide a heritable basis for alternative reproductive tactics motivated by reduced sperm competitiveness. We discuss how experimental and evolutionary constraints may help explain why male genotypes did not show the predicted differences.
R2d2 drives selfish sweeps in the house mouse
4084Didion, JPM, A. P.; Yadgary, L.; Bell, T. A.; McMullan, R. C.; de Solorzano, L. O.; Britton-Davidian, J.; Bult, C. J.; Campbell, K. J.; Castiglia, R.; Ching, Y. H.; Chunco, A. J.; Crowley, J. J.; Chesler, E. J.; Forster, D. W.; French, J. E.; Gabriel, S. I.; Gatti, D. M.; Garland, T.; Giagia-Athanasopoulou, E. B.; Gimenez, M. D.; Grize, S. A.; Gunduz, I.; Holmes, A.; Hauffe, H. C.; Herman, J. S.; Holt, J. M.; Hua, K. J.; Jolley, W. J.; Lindholm, A. K.; Lopez-Fuster, M. J.; Mitsainas, G.; Mathias, M. D.; McMillan, L.; Ramalhinho, M. D. M.; Rehermann, B.; Rosshart, S. P.; Searle, J. B.; Shiao, M. S.; Solano, E.; Svenson, K. L.; Thomas-Laemont, P.; Threadgill, D. W.; Ventura, J.; Weinstock, G. M.; Pomp, D.; Churchill, G. A.; de Villena, F. P. M., Molecular Biology and Evolution, 33:1381-1395. 2016-01-02 00:00:00.
A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding inmultiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.
The Trojan Female Technique for pest control: a candidate mitochondrial mutation confers low male fertility across diverse nuclear backgrounds in Drosophila melanogaster
13733D. K. Dowling, D. M. Tompkins and N. J. Gemmell, Evolutionary Applications, 8:8710880. 2015-07-15 19:28:56.
The Trojan Female Technique (TFT) was recently proposed as a prospective approach to biological pest control. However, applicability of the TFT relies on mitochondrial mutations whose male-sterilizing effects are general across nuclear genomic contexts. We test this assumption, expressing the candidate TFT-mutation bearing haplotype alongside a range of nuclear backgrounds and comparing its fertility in males, relative to that of control haplotypes
Detrimental effects of an autosomal selfish genetic element on sperm competitiveness in house mice
4126Sutter, AL, A. K., Proceedings of the Royal Society B-Biological Sciences, 282:1-8. 2015-01-04 00:00:00.
Female multiple mating (polyandry) is widespread across many animal taxa and indirect genetic benefits are a major evolutionary force favouring polyandry. An incentive for polyandry arises when multiple mating leads to sperm competition that disadvantages sperm from genetically inferior mates. A reduction in genetic quality is associated with costly selfish genetic elements (SGEs), and studies in invertebrates have shown that males bearing sex ratio distorting SGEs are worse sperm competitors than wild-type males. We used a vertebrate model species to test whether females can avoid an autosomal SGE, the t haplotype, through polyandry. The t haplotype in house mice exhibits strong drive in t heterozygous males by affecting spermatogenesis and is associated with homozygous in utero lethality. We used controlled matings to test the effect of the t haplotype on sperm competitiveness. Regardless of mating order, t heterozygous males sired only 11% of zygotes when competing against wild-type males, suggesting a very strong effect of the t haplotype on sperm quality. We provide, to our knowledge, the first substantial evidence that polyandry ameliorates the harmful effects of an autosomal SGE arising through genetic incompatibility. We discuss potential mechanisms in our study species and the broader implications for the benefits of polyandry.
Centromere strength provides the cell biological basis for meiotic drive and karyotype evolution in mice
4137Chmatal, LG, S. I.; Mitsainas, G. P.; Martinez-Vargas, J.; Ventura, J.; Searle, J. B.; Schultz, R. M.; Lampson, M. A., Current Biology, 24:2295-2300. 2014-01-15 00:00:00.
Mammalian karyotypes (number and structure of chromosomes) can vary dramatically over short evolutionary time frames [1-3]. There are examples of massive karyotype conversion, from mostly telocentric (centromere terminal) to mostly metacentric (centromere internal), in 102-10 s years [4, 5]. These changes typically reflect rapid fixation of Robertsonian (Rb) fusions, a common chromosomal rearrangement that joins two telocentric chromosomes at their centromeres to create one metacentric [5]. Fixation of Rb fusions can be explained by meiotic drive: biased chromosome segregation during female meiosis in violation of Mendel's first law [3, 6, 7]. However, there is no mechanistic explanation of why fusions would preferentially segregate to the egg in some populations, leading to fixation and karyotype change, while other populations preferentially eliminate the fusions and maintain a telocentric karyotype. Here we show, using both laboratory models and wild mice, that differences in centromere strength predict the direction of drive. Stronger centromeres, manifested by increased kinetochore protein levels and altered interactions with spindle microtubules, are preferentially retained in the egg. We find that fusions preferentially segregate to the polar body in laboratory mouse strains when the fusion centromeres are weaker than those of telocentrics. Conversely, fusion centromeres are stronger relative to telocentrics in natural house mouse populations that have changed karyotype by accumulating metacentric fusions. Our findings suggest that natural variation in centromere strength explains how the direction of drive can switch between populations. They also provide a cell biological basis of centromere drive and karyotype evolution.
Meiotic drive in mice carrying t-complex in their genome
4180Safronova, LDC, V. L., Russian Journal of Genetics, 49:885-897. 2013-01-18 00:00:00.
The deviation of alleles and chromosomes from Mendelian inheritance is characteristic of the meiotic drive. This review describes the mechanism in question using the best-studied example of transmitted ratio distortion in the heterozygous male mice carrying t-haplotypes. The t-complex is best model for studying the meiotic drive under laboratory conditions. Putative mechanisms of meiotic drive that influence the frequency of t-haplotypes in natural populations are considered, of which prezygotic selection is the most important. The role of meiotic drive in male hybrid sterility is emphasized. The factors and models that determine the phenomenon of meiotic drive are discussed in detail.
Maternal transmission ratio distortion at the mouse Om locus results from meiotic drive at the second meiotic division
4283Wu, GMH, L. P.; Han, Z. M.; Gao, S. R.; Latham, K. E.; de Villena, F. P. M.; Sapienza, C., Genetics, 170:327-334. 2005-01-21 00:00:00.
We have observed maternal transmission ratio distortion (TRD) in favor of DDK alleles at the Ovum mutant (Om) locus on mouse chromosome I I among the offspring of (C57BL/6 X DDK) F, females and C57BL/6 males. Although significant lethality occurs in this backcross (similar to 50%), differences in the level of TRD found in recombinant vs. nonrecombinant chromosomes among offspring argue that TRD is due to nonrandom segregation of chromatids at the second meiotic division, i.e., true meiotic drive. We tested this hypothesis directly, by determining the centromere and Om genotypes of individual chromatids in zygote stage embryos. We found similar levels of TRD in favor of DDK alleles at Om in the female pronucleus and TRD in favor of C57BL/6 alleles at Om in the second polar body. In those embryos for which complete dyads have been reconstructed, TRD was present only in those inheriting heteromorphic dyads. These results demonstrate that meiotic drive occurs at MII and that preferential death of one genotypic class of embryo does not play a large role in the TRD.
Physical mapping of male fertility and meiotic drive quantitative trait loci in the mouse t complex using chromosome deficiencies
4345Planchart, AY, Y.; Schimenti, J. C., Genetics, 155:803-812. 2000-01-03 00:00:00.
The t complex spans 20 cM of the proximal region of mouse chromosome 17. A variant form, the t haplotype (t), exists at significant frequencies in wild mouse populations and is characterized by the presence of inversions that suppress recombination with Mild-type (+) chromosomes. Transmission ratio distortion and sterility are associated with t and affect males only. It is hypothesized that these phenomena are caused by trans-acting distorter/sterility factors that interact with a responder locus (Tcr(t)) and that the distorter and sterility factors are the same because homozygosity of the distorters causes male sterility. One factor, Tcd1, was previously shown to be amorphic using a chromosome deletion. To overcome limitations imposed by recombination suppression, we used a series of deletions within the t complex in trans to t chromosomes to characterize the Tcd1 region. The find that the distorter activity of Tcd1 is distinct from a linked sterility factor, originally called tcs1. YACs mapped with respect to deletion breakpoints localize tcs1 to a 1.1-Mb interval flanked by D17Aus9 and Tctex1. We present evidence for the existence of multiple proximal t complex regions that exhibit distorter activity. These studies demonstrate the utility of chromosome deletions for complex trait analysis.
Segregation distortion in unstructured and structured populations: Competition between ‘sterile’ t haplotypes
4403VanBoven, MW, F. J., Netherlands Journal of Zoology, 46:216-226. 1996-01-21 00:00:00.
By means of two simple models we investigate the competition between sex-specific segregation distorters in unstructured and structured populations. The models are motivated by the t complex of the house mouse. Some variants at this gene complex, the t haplotypes, distort Mendelian segregation in their favour in heterozygous males. The selective advantage at the gamete level is counterbalanced by strong negative fitness effects at the individual level. A large number of t haplotypes with varying degrees of segregation distortion has been found. In order to address this phenomenon we explicitly model the competition between two t haplotypes which induce male sterility when homozygous. Surprisingly, a distorter which is inferior at the gamete level and equivalent in every other respect to a more efficient distorter may well persist in a population. We argue that rare distorters are inherently favoured, and that, as a result, fitness considerations alone are not sufficient to predict the outcome of competition. Since 'sterile' t haplotypes are not only influenced by gamete and individual selection, but also by selection at the level of the group, we furthermore study the relation between unstructured and structured populations. It is shown that the persistence of a seemingly inferior distorter is also possible in a structured population. In contrast, a single efficient distorter with high segregation ratio may not even be able to persist in a structured population. Hence, in a metapopulation with migration between local demes, the segregation ratio is an even worse predictor of the evolutionary success of a segregation distorter than in an unstructured population.
Competition between segregation distorters: Coexistence of ”superior” and ”inferior” haplotypes at the t complex
4402vanBoven, MW, F. J.; Heg, D.; Huisman, J., Evolution, 50:2488-2498. 1996-01-20 00:00:00.
By means of population genetical models, we investigate the competition between sex-specific segregation distorters. Although the models are quite general, they are motivated by a specific example, the t complex of the house mouse. Some variants at this gene complex, the t haplotypes. distort Mendelian segregation in heterozygous males in their favor. The selective advantage at the gamete level is counterbalanced by strong negative fitness effects at the individual level (male sterility or even lethality in both sexes). A plethora of different t haplotypes has been found, both in the field and in the lab. Up to now, however, models have focused on the equilibrium frequency of a single t haplotype. In contrast, we explicitly model the competition between several t haplotypes, A deterministic model for a large, well-mixed population predicts a surprisingly high degree of polymorphism. Haplotypes with seemingly inferior fitness characteristics may easily coexist with ''superior'' haplotypes. For instance, a lethal haplotype with a low segregation ratio may stably coexist with a sterile haplotype with a high segregation ratio, Stable coexistence is even possible for haplotypes with a segregation disadvantage. A simple stochastic model shows that the same principles apply in the context of a structured metapopulation. Although counterintuitive at first sight, all our results can be explained by the fact that segregation distorters have an inherent advantage when they are rare. We conclude that fitness comparisons are not sufficient to predict the outcome of competition when selective forces are acting at different levels.
Meiotic drive in female mice: An essay
4407Ruvinsky, A, Mammalian Genome, 6:315-320. 1995-01-05 00:00:00.
Since the rediscovery of Mendel's laws, geneticists have accumulated various examples in which equal meiotic segregation in heterozygotes is violated. However, only a few natural meiotic drive systems have been characterized in detail and the majority of these are sex chromosome linked (Hurst and Pomiankovski 1991a). In animals, only two autosomal meiotic drive systems have been thoroughly investigated: the t complex in Mus musculus (Lyon 1991; Silver 1993) and the Segregation Distorter system (SD) in Drosophila melanogaster (Lyttle 1991). Both affect heterozygous males. Recently Agulnik and associates (1990a, 1993c, 1993d) have found and described a new meiotic drive system that disturbs normal segregation in heterozygous female mice. The system is the main target of this review, which also includes a comparative analysis of other drive systems to establish a likely scenario of their origin, evolution, and stability in natural populations.
Meiotic drive of t haplotypes: chromosome segregation in mice with tertiary trisomy
4434Agulnik, AIA, Sergei I.; Ruvinsky, Anatoly O., Genetics Research, 57:51. 1991-01-12 00:00:00.
The properties of the / haplotypes, specific mutant states of the proximal region of chromosomes17 in the house mouse, are of continuing interest. One such property is increased transmission ofthe / haplotype by heterozygous // + males to offspring. Using the reciprocal translocationT(16; 17)43H we have constructed males with tertiary trisomy of chromosome 17( + T43/+ +/Rb7 + ) carrying the Robertsonian translocation Rb(16.17)7Bnr. Only the progeny ofthese males which had inherited either T43/ + or Rb7 from their male parent were viable. Thesegregation patterns in the offspring of /-bearing trisomics were analysed on days 16-18 ofembryonic development. It was found that, when the tn haplotype is in the normal acrocentric(c?c?+ + T43/ + //2+/Rb7 + +), its presence in the gamete +/" + /+ + T43 does not producemeiotic drive. However, when t6 is in Rb7, meiotic drive was observed: 80 % of offspring carriedthe / haplotype. It is concluded that the meiotic drive is probably inhibited by the presence of anormal homologue of chromosome 17 in the same sperm. Possible mechanisms for the t haplotypeeffect are discussed
Studies of the genetic variability in populations of wild house mice .2. Analysis of eight additional alleles at locus – T
6113L. C. Dunn, Genetics, 42:299-311. 1957-01-02 19:27:44.
1 Eight additional lethal alleles at locus T are described, each derived from a wild heterozygote in one of six different wild populations. 2. The frequency of heterozygotes appears to be high in most wild populations, possibly as high as 50 percent. 3. In two of the populations in which several heterozygotes were found, the same allele was isolated from each heterozygote of the same population. One heterozygote was found in each of two subpopulations on the same farm. These two alleles have not been shown to be different. One wild heterozygote from another population transmitted two different alleles; probably one was a new mutant, giving rise to the possibility that more than one allele may occur in the same population, although the rule at present is to find but one type of variant allele per population. 4. All wild t alleles show the “male segregation ratio peculiarity” by which male heterozygotes transmit the t allele to a great majority (about 96 percent) of the offspring. This may be due to the effects of natural selection on factors favoring high transmission ratios. 5. t alleles from the wild fall into at least three groups, one with three viable alleles, and two groups of lethals. Lethals within the same group have not formed viable compounds when combined; lethals belonging to different groups do form viable compounds by complementary interaction and are thus shown to be nonidentical. 6. Since 29 alleles have now been detected at this locus, many of which are nonidentical, the locus is assumed to contain many sites of mutation and to have great potential complexity.
Sur la reproduction des souris anoures
6057N. Dobrovolskaia-Zavadskaia and N. Kobozieff, Comptes rendus des séances de la Société de biologie et de ses filiales, 97:116-119. 1927-06-15 15:44:03.
Nous ne connaissons que deux lignees de Souris sans queue, celle de Lang (1913), et cell de Duboscq (1922). L’elevange de Lang (lignee des Souris brachyures et anoures du preparateur Alfred Nageli) a donne 199 Souris normales, pour 173 brachyures et 9 anoures. Croisses entre ells et aveec des bachyures, les Souris anoures n’ont donne aucune reproduction. Dans la lignee du P Duboscq, provenant d’une femelle anoure A et de son frere normal, et comportant 25 petis en 8 portees, il y avait 8 anoures, don’t la plupart moururent jeunes.
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