Keywords: Ecology
A conjugal gene drive-like system efficiently suppresses antibiotic resistance in a bacterial population
35426Kaduwal, S., Stuart, E.C., Auradkar, A. et al., npj Antimicrobials and Resistance, 4. 2026-02-05 10:30:00.
Antibiotic resistance (AR) is an escalating public health threat, necessitating innovative strategies to control resistant bacterial populations. One promising approach involves engineering genetic elements that can spread within microbial communities to eliminate AR genes. Previously, we developed Pro-Active Genetics (Pro-AG), a CRISPR-based gene-drive-like system capable of reducing AR colony-forming units (CFU) by approximately five logs. Here, we advance this technology by integrating Pro-AG into a conjugative transfer system, enabling efficient dissemination of an anti-AR gene cassette between two bacterial strains. Additionally, we characterize a complementary homology-based deletion (HBD) process, a CRISPR-driven mechanism that precisely removes target DNA sequences flanked by short direct repeats. Our findings reveal that Pro-AG and HBD are differentially influenced by the bacterial RecA pathway and that HBD components can be delivered via plasmids or phages to selectively delete Pro-AG cassettes. This built-in safeguard prevents uncontrolled spread of a gene cassette and mitigates unanticipated side effects. These refinements enhance the efficiency and flexibility of Pro-AG, expanding its potential applications in microbiome engineering, environmental remediation, and clinical interventions aimed at combating antibiotic resistance. More broadly, this work establishes a proof-of-principle for microbiome engineering strategies that could be leveraged to improve health and restore ecological balance.
Serratia species as paratransgenic vehicles: potential applications in vector-borne disease control
35422Mahor S, Gupta H. 0., Clinical Microbiology Reviews, 2026-02-02 15:13:09.
Paratransgenesis employs insect-associated bacteria to deliver antipathogen effectors and is an emergent complementary strategy for vector control. This review synthesizes current evidence for Serratia species as paratransgenic vehicles, combining mechanistic insights into effector molecules (e.g., scorpine, MP2, multi-fusion constructs, and the naturally secreted antimalarial lipase AmLip), with comparative evidence on colonization, transmission, and efficacy. Serratia strains (e.g., AS1, Su_YN1) demonstrate rapid dissemination in laboratory populations and potent reductions in Plasmodium development (reported oocyst inhibition in laboratory studies ranging from ~60% to >90% for specific effectors). We critically examine biosafety, genetic stability, and ecological factors and propose a minimum evidence package and translational roadmap comprising multigeneration stability assays, horizontal gene transfer monitoring, non-target impact assessments, and community and regulatory engagement to responsibly advance Serratia-based paratransgenesis toward field evaluation. This comparative framing integrates Serratia-focused detail with the broader paratransgenesis literature to clarify both its promise and remaining knowledge gaps.
Three Stunning Ways Biologists Aim to Edit Animal and Plant Genes to Fight Diseases and Extinction
35386Sandy Ong, Smithsonian Magazine, 2026-01-21 16:42:41.
In the summer of 1904, Herman Merkel, chief forester at the Bronx Zoo, in New York City, was making his usual rounds across the property when he noticed something strange growing on American chestnut trees: misshapen constellations of swollen, orange-brown cankers. Unbeknownst to Merkel, his observations were the first signs of what would later be referred to as “the greatest ecological disaster in North America since the Ice Age.” Further investigation revealed that the culprit was a fungus called Cryphonectria parasitica, or chestnut blight, which slips its spores through cracks in the bark and fatally severs a tree’s water and nutrient supply. The pathogen was a stowaway that had arrived on imported Japanese chestnut trees, which are resistant—but on American soil, it proved to be a swift and merciless killer. Barely a year later, the blight had claimed nearly all the zoo’s chestnuts—as well as those in the surrounding Bronx parks. By the 1950s, it had wiped out 99 percent of the species’ population across the Eastern United States, where more than four billion of the towering trees had once so blanketed the landscape that a squirrel was said to be able to travel from Maine to Georgia on chestnut branches alone. Since then, scientists have tried, with little success, to bring the trees back from the brink. Today, American chestnuts are considered functionally extinct. Full-sized trees are hard to come by; mainly roots and shoots remain. Scientists have bred hybrid American-Chinese chestnut trees, but planting fully native species is important for ecological restoration goals, says Andrew Newhouse, director of the American Chestnut Research and Restoration Project at the State University of New York (SUNY). Thanks to an emerging field, the iconic trees—and other imperiled species—could one day be restored. The discipline, called synthetic biology, relies on editing organisms’ DNA to introduce new genes or modify existing ones, essentially reprogramming life to fight disease, clean up the environment, increase food production and more. For chestnut trees, making changes to their genome could boost their resistance to the blight.
Gene drives, species complexes, and the risks of collateral damage
35296C. Boëte, Proc. Natl. Acad. Sci., 122. 2025-11-09 18:26:26.
The development of engineered gene drive systems continues to garner significant interest. Theoretically, these systems could spread traits in a target species (an approach known as population replacement) or eliminate a population within a few generations (population suppression). Some researchers have promoted this disruptive technology for potential applications ranging from public health (e.g., malaria control) to conservation (e.g., protection of endangered species, elimination of invasive ones) to agriculture (e.g., pest control). But in the case of a gene drive intended to target a specific species, the risk of affecting non-target species must be taken into account, and researchers must strive to minimize collateral damage. Hybridization between a target and a non-target species could result in unintended gene flow, as could the horizontal transfer of the gene drive cassette (1). While some researchers have proposed the “Target Species Complex” (TSC) framework to account for off-target effects, the concept is unlikely to provide a safeguard. Rather, it risks reframing collateral impacts as intentional outcomes, narrowing, rather than broadening, the scope of ecological and regulatory considerations. Researchers must therefore make sure to incorporate risk assessments that take into account the effects on numerous species and make a concerted effort to understand the downstream effects.
Biotechnology Is a Powerful Tool for Conservation
35205Emma Kovak, The Ecomodernist, 2025-09-30 15:40:23.
What do the American Chestnut tree, the black rat, and the northern white rhinoceros have in common? They are all prime targets for conservation through biotechnology. Genetic engineering could give American chestnut trees disease resistance and restore the keystone species to Eastern forests, gene drives could eliminate rats from islands and save seabirds from the invasive predators, and assisted reproduction technology could rescue the Northern white rhinoceros from the brink of extinction. The U.S. Department of Agriculture is poised to approve an American chestnut engineered to resist the blight that functionally eliminated the species from Eastern forests. Meanwhile, the International Union for Conservation of Nature (IUCN)—the world’s largest conservation network—is voting on whether to ban biotechnology outright or recommend thoughtful case-by-case evaluation. These decisions are important determinants of biotechnology’s role in the conservation toolkit. With extinction rates accelerating, conservation efforts should be able to use as many tools as possible.
Should we edit nature?
35176David Farrier, Aeon, 2025-09-26 14:10:35.
At the end of August 1939, the German archaeologist Otto Völzing discovered around 200 fragments of carved mammoth ivory at the back of a cave in southern Germany. With war just a week away, Völzing’s find was hurriedly collected in a box, where it lay unnoticed in a museum archive for decades. It wasn’t until the 1960s, when the shards were inventoried, that something astonishing emerged out of the heap of broken pieces. They formed an incomplete figurine, with a chimeric mix of features: the body of person, and the head and forearms of a cave lion. Subsequent excavations in the 1970s found further pieces of what has come to be called the Lion-Man of Hohlenstein-Stadel. Carved from a mammoth tusk around 40,000 years ago, it is one of the earliest examples of the human capacity to imagine forms that don’t exist in nature. Every age of human history since the Lion-Man has tried to think beyond nature. In Hesiod’s Theogony, composed around 700 BCE, the chimera was a compound being with the head of a lion, the body of a dragon, and a snake’s-head tail (and an extra goat’s head protruding from its back for good measure). In W B Yeats’s poem ‘The Second Coming’ (1920), a similar ‘rough beast’ is a harbinger of ruin. In our own time, the chimeras are something different. Living things in every part of the biosphere have been forced by climate change, pollution and the spread of non-native species to adapt their bodies and behaviours to a human planet. They may not have visibly merged forms like the Lion-Man, but they do bear the impression of another species: us.
Are we winning the war on cane toads?
35089Tom Gurn, Particle, 2025-08-28 19:10:42.
In 1935, a species known as the giant neotropical toad (Rhinella marina) was introduced to Australia. Scientists hoped these amphibians would control native cane beetles, but cane toads quickly colonised the country and had no discernible impact on beetle populations. Many different methods are being tested to remove these warty beasts, including a toad containment zone and turning the toads into sausages. Now, almost a century later, scientists believe they have finally stumbled across a potential solution to one of the worst invasive species ever. Will clever gene-editing techniques finally rid this continent of the dreaded cane toad? Professor Emeritus Rick Shine led the team behind the new idea, based on CRISPR gene-editing techniques. “We seem to have found a chink in the toads’ armour,” says Rick. “If we could only stop their metamorphosing, we could have these eternal tadpoles,” he says. Searching for collaborators to test this cunning plan, Rick happened across molecular biologist Dr Maciej Masielko, who was immediately struck by the beauty of the idea. “We know enough about the biochemistry of metamorphosis to know what we would need to do,” says Maciej. “Like using CRISPR-Cas9 to delete a part of the cane toad’s DNA.”
Growth and development of two predator species fed a diet of genetically engineered mosquitoes
35081Egan, C.M., Chamberland, L., Ditter, R.E. et al., Parasites Vectors, 18. 2025-08-28 16:18:12.
Genetically engineered mosquitoes (GEMs) with gene drives have been developed for malaria control but remain untested in natural environments. Upon release, GEMs are expected to modify or replace wild-type counterparts, potentially uniquely interacting with nontarget organisms (NTOs). Concerns exist over possible negative effects on NTOs and broader ecological harm. Predators consuming GEMs represent a group that interacts closely with these modified mosquitoes. Here, we examine the effect of GEM and wild-type Anopheles coluzzii diets on the growth of two predator species: the aquatic mosquitofish (Gambusia affinis) and the terrestrial bold jumping spider (Phidippus audax). Gambusia affinis was fed lyophilized gravid mosquitoes, and growth was measured using length and mass. Phidippus audax was fed live semi-gravid mosquitoes, with growth tracked via eye size, body size, and mass. No adverse effects were found in either predator species fed GEM diets. Gambusia affinis showed no significant growth differences between diet groups. However, P. audax that were fed GEMs consumed more mosquitoes, grew larger, and matured faster. Differences in predator growth rate suggest that GEMs’ nutritional content is similar to that of wild-type mosquitoes, but that they may be more vulnerable to predation. Further research is needed to explore whether GEM visual or behavioral traits increase their susceptibility to predators.
Ecology and evolution in gene drive modeling
35060NSF-Simons NITMB, YouTube, 2025-08-25 16:09:18.
Speaker: Gili Greenbaum Title: Ecology and evolution in gene drive modeling This talk was recorded as part of the Modeling and Theory in Population Biology workshop at NITMB. The NSF-Simons National Institute for Theory and Mathematics in Biology (NITMB) aims to integrate the disciplines of mathematics and biology in order to transform the practice of biological research and to inspire new mathematical discoveries. NITMB is a partnership between Northwestern University and the University of Chicago. It is funded by the National Science Foundation DMS-2235451 and the Simons Foundations MP-TMPS-00005320. The mission of the NITMB is to create a nationwide collaborative research community that will generate new mathematical results and uncover the “rules of life” through theories, data-informed mathematical models, and computational and statistical tools. The NITMB leverages close collaborations between experimentalists and theorists to synergize discovery. The fundamental research done by NITMB will stimulate advances in areas as diverse as the environment, medicine, and technology development. NITMB members and visitors share space in downtown Chicago that is readily accessible to collaborators across the U.S. and the world. NITMB uses an interlocking set of strategies and initiatives aimed at broad impacts for the mathematical and biological research communities. Targeted research bringing together mathematicians and biologists to collaborate and train the next generation of interdisciplinary scientists. Scientific long programs, workshops, and conferences enhancing collaboration between mathematics and biology. An innovative research program organized around five interrelated themes, selected because they reflect key capabilities of biological systems and interconnect with open mathematical problems.
Rollins presses ahead with latest initiative on New World screwworm
34924HPJ staff, High Plains Journal, 2025-06-19 14:41:39.
U.S. Secretary of Agriculture Brooke Rollins on June 18 announced an $8.5 million sterile New World screwworm fly dispersal facility in south Texas and a five-pronged plan to enhance the U.S. Department of Agriculture’s ability to detect, control and eliminate the pest. In a media release, the USDA noted actions are necessary to finish the fight against NWS and protect the United States. NWS is a devastating pest that causes serious and often deadly damage to livestock, wildlife, pets, and in rare cases, humans. While NWS has been eradicated from the U.S. for decades, recent detections in Mexico as far north as Oaxaca and Veracruz, about 700 miles away from the U.S. border, led to the immediate suspension of live cattle, horse and bison imports through U.S. ports of entry along the southern border on May 11. “The United States has defeated NWS before and we will do it again,” Rollins said. “We do not take lightly the threat NWS poses to our livestock industry, our economy, and our food supply chain. The United States government will use all resources at its disposal to push back NWS, and today’s announcement of a domestic strategy to bolster our border defenses is just the beginning. We have the proven tools, strong domestic and international partnerships, and the grit needed to win this battle.”
The Future of Gene Drive in Farming
34895Sarah Lee, Number Analytics, 2025-06-06 08:25:42.
The advent of gene drive technology has opened up new avenues for transforming farming practices, improving crop yields, and promoting sustainability. Gene drive is a genetic engineering technique that allows for the rapid spread of a particular gene or trait through a population, potentially revolutionizing the way we approach crop improvement and pest management. In this article, we will explore the latest advancements in gene drive technology and its potential to shape the future of farming. Gene drive has the potential to significantly improve crop yields and nutritional content by introducing desirable traits such as pest resistance, drought tolerance, and enhanced nutritional profiles. The development of pest-resistant crops, for instance, could reduce the need for pesticides, minimizing the environmental impact of farming practices. Gene drive can be used to introduce genes that confer resistance to pests and diseases, reducing crop losses and improving yields. For example, scientists have used gene drive to develop mosquitoes that are resistant to malaria. Similarly, gene drive can be used to enhance the nutritional content of crops, such as by introducing genes that increase the production of essential micronutrients like vitamin A.
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.
Applications and status of gene drive in plants
34771Hay BA, PLOS Biology, 23. 2025-04-18 10:06:07.
Globalization—the movement of humans, plants, animals, and microbes—together with climate change, place numerous plant and animal species under novel stresses. For plants, threats include global warming, invasive species, weeds, animal pests, and vectors of disease. Harms can be mitigated or prevented through population-scale genetic alterations that introduce beneficial traits such as disease resistance or drought tolerance (population modification), or that eliminate a harmful population (population suppression). Gene drive is a possible tool for achieving these goals. DNA mediating gene drive comprises one or more genes (the drive element) that promote their own inheritance—and any linked cargo—at rates exceeding (>50%) those of other genes. This can lead to an increase in drive element frequency even if its presence results in a fitness cost to carriers. Gene drive is attractive because it is self-amplifying and self-sustaining. One class of gene drive utilizes a Toxin-Antidote (TA) element. In nature, these often consist of two tightly linked protein-encoding genes. One encodes a toxin that is inherited by all gametes and/or progeny of a carrier; the second is an antidote that protects carriers from death. The TA element-bearing chromosome gains a relative transmission advantage by causing death of those who fail to inherit it. The first synthetic gene drive was engineered using TA logic, in Drosophila melanogaster in 2007. Recently, TA logic was also used to create the first synthetic gene drive elements in plants, in Arabidopsis thaliana. These use a Cleave and Rescue mechanism (ClvR) adapted from earlier work in Drosophila. ClvR uses DNA cleavage mediated by Cas9 and guide RNAs (gRNAs), followed by inaccurate repair, to create loss-of-function (LOF) alleles (the toxin) of endogenous versions of an essential gene. ClvR also includes a Rescue version of the essential gene recoded to prevent gene disruption (the antidote), which guarantees survival of carriers. In Drosophila, ClvR spreads because LOF alleles created in parents cause the death of progeny who lack essential gene function. In Arabidopsis this strategy was used to create gamete killers. A naturally occurring male gamete killer from rice, DUYAO-JIEYAO, consists of a two-gene protein–protein TA cassette. Modeling suggests that gamete killers such as these can bring about population modification or suppression. Interestingly, the DUYAO-JIEYAO element has undergone a substantial increase in frequency in Japonica rice populations in China over the last 50 years, demonstrating the power of such elements in nature.
Experts: One Health approach to help combat zoonotic diseases in Africa
34728Milliam Murigi, People Daily, 2025-03-31 16:41:28.
If African countries are to successfully combat zoonotic diseases, human health, animal health, and environmental health must be treated as one interconnected system. This was revealed in Accra, Ghana, during the second global congress on new and emerging genetic biocontrol technologies. Speaking during the meeting, Misheck Mulumba, the congress president said that, there is no way Africa is going to win this fight if different departments keep seeing rise of zoonotic diseases as a problem for one department and not their mandate. “It is important that different practitioners in all the three departments to work together to combat these infections. These three departments should stop pointing fingers but should instead work together to solve the problems the continent has,” Mulumba said noting Africa must embrace One Health approach. One Health approach is a collaborative, multisectoral, and trans disciplinary strategy that recognizes the interconnection between human health, animal health, and the environment. It emphasises that diseases affecting humans often originate from animals and are influenced by environmental factors, making it essential for experts from different fields such as medicine, veterinary science, environmental science, and public health to work together to prevent and control health threats. With 75 per cent of emerging and reemerging diseases originating from animals, Mulumba notes, it’s clear that tackling these infections requires a collaborative approach. Apart from that, the continent needs to invest in rapid detection, response, and control mechanisms to curb disease outbreaks before they escalate into global health emergencies.
Wolbachia-based mosquito control: Environmental perspectives on population suppression and replacement strategies
34543Bhattacharyya, J., Roelke, D.L., Acta Tropica, 262. 2025-02-25 10:59:30.
Mosquito-borne diseases pose a significant threat to global health, and traditional mosquito control methods often fall short of effectiveness. A promising alternative is the biological control strategy of transinfecting mosquitoes with Wolbachia, a bacterium capable of outcompeting harmful pathogens and reducing the ability of mosquitoes to transmit diseases. However, Wolbachia infections are sensitive to abiotic environmental factors such as temperature and humidity, which can affect their densities in mosquitoes and, consequently, their ability to block pathogens. This review evaluates the effectiveness of different Wolbachia strains transinfected into mosquitoes in reducing mosquito-borne diseases. It explores how Wolbachia contributes to mosquito population control and pathogen interference, highlighting the importance of mathematical models in understanding Wolbachia transmission dynamics. Additionally, the review addresses the potential impact on arboviral transmission and the challenges posed by environmental fluctuations in mosquito control programs.
Progress made for blackchin tilapia control in Thailand
34535The Fish Site, 2025-02-21 11:50:45.
Despite tilapia being one of the most widely farmed fish in the global aquaculture industry, invasive populations of the blackchin tilapia - a cichlid native to West Africa - have been devastating the productivity of aquaculture operations throughout Thailand. However, a multi-stakeholder effort led by the country's Department of Fisheries has reported progress towards controlling this invasive species, turning an environmental challenge into a pathway for sustainable development and local economic growth. Forming part of a five-point government strategy to address the ecological challenges posed by invasive species, the Department of Fisheries has developed a specially engineered strain known as Blackchin Tilapia 4n - a genetically modified variant designed to inhibit reproduction. The experimental strain has been released at experimental sites this month to evaluate its effectiveness in reducing the invasive fish population. Simultaneously, another project is specifically geared towards assisting aquaculture producers. The Seabass Fund for Farmers assists farmers in reducing costs by introducing natural predators into aquaculture ponds, effectively managing the blackchin tilapia population. This programme was established by the Phetchaburi Provincial Fisheries Office to support small-scale farmers with revolving funds for purchasing seabass fingerlings, providing a sustainable solution for shrimp, fish, and crab farmers operating in semi-natural systems to control and reduce populations of the invasive cichlid. In addition to direct eradication efforts, the promotion of blackchin tilapia products, such as foods and feeds, is being used to encourage consumption of the fish, driving local economic growth. These initiatives have been implemented by Charoen Pokphand Foods throughout 2024, including the purchase of 2 million kilograms of Blackchin tilapia for fishmeal production. Charoen Pokphand has also extended assistance to fishing activities aimed at blackchin tilapia removal by supplying fishing equipment and necessary materials to participants. If successful, these programmes for the control of blackchin tilapia populations in Thailand could serve as a model for governmental and private-sector cooperation for environmental solutions and local economic development.
Wolbachia-Based Approaches to Controlling Mosquito-Borne Viral Threats: Innovations, AI Integration, and Future Directions in the Context of Climate Change
34249Branda, F., Cella, E., Scarpa, F., et al., Viruses, 16:1868. 2025-01-13 14:55:50.
Wolbachia-based mosquito control strategies have gained significant attention as a sustainable approach to reduce the transmission of vector-borne diseases such as dengue, Zika, and chikungunya. These endosymbiotic bacteria can limit the ability of mosquitoes to transmit pathogens, offering a promising alternative to traditional chemical-based interventions. With the growing impact of climate change on mosquito population dynamics and disease transmission, Wolbachia interventions represent an adaptable and resilient strategy for mitigating the public health burden of vector-borne diseases. Changes in temperature, humidity, and rainfall patterns can alter mosquito breeding habitats and extend the geographical range of disease vectors, increasing the urgency for effective control measures. This review highlights innovations in Wolbachia-based mosquito control and explores future directions in the context of climate change. It emphasizes the integration of Wolbachia with other biological approaches and the need for multidisciplinary efforts to address climate-amplified disease risks. As ecosystems shift, Wolbachia interventions could be crucial in reducing mosquito-borne diseases, especially in vulnerable regions. AI integration in Wolbachia research presents opportunities to enhance mosquito control strategies by modeling ecological data, predicting mosquito dynamics, and optimizing intervention outcomes. Key areas include refining release strategies, real-time monitoring, and scaling interventions. Future opportunities lie in advancing AI-driven approaches for integrating Wolbachia with other vector control measures, promoting adaptive, data-driven responses to climate-amplified disease transmission.
Wolbachia-based mosquito control: Environmental perspectives on population suppression and replacement strategies
34213Joydeb Bhattacharyya, Daniel L. Roelke, Acta Tropica, 262. 2025-01-07 09:07:50.
Mosquito-borne diseases pose a significant threat to global health, and traditional mosquito control methods often fall short of effectiveness. A promising alternative is the biological control strategy of transinfecting mosquitoes with Wolbachia, a bacterium capable of outcompeting harmful pathogens and reducing the ability of mosquitoes to transmit diseases. However, Wolbachia infections are sensitive to abiotic environmental factors such as temperature and humidity, which can affect their densities in mosquitoes and, consequently, their ability to block pathogens. This review evaluates the effectiveness of different Wolbachia strains transinfected into mosquitoes in reducing mosquito-borne diseases. It explores how Wolbachia contributes to mosquito population control and pathogen interference, highlighting the importance of mathematical models in understanding Wolbachia transmission dynamics. Additionally, the review addresses the potential impact on arboviral transmission and the challenges posed by environmental fluctuations in mosquito control programs.
Pest control gets the CRISPR treatment
33376Seydel, C., Nature Biotechnology, 2024-11-04 13:45:02.
In June 2024, the St. Louis–based pest control company Agragene released genetically modified fruit flies on berry farms in California and Oregon, moving the technology out of the laboratory and into contained field testing. The trial marked a milestone for a next-generation biocontrol technology called the precision-guided sterile insect technique, or pgSIT. “The spotted wing drosophila (SWD) is the number 1 problem for any kind of strawberry, blueberry, raspberry, blackberry grower,” said Bryan Witherbee, president and CEO of Agragene. The flies have developed resistance to conventional chemical pesticides, and fruit growers suffer enormous economic losses due to the pest. “Growers are crying out for new tools,” Witherbee said. Hope is on the horizon, not only for farmers battling SWD and other agricultural pests but also for public health agencies struggling to control disease vectors. Several companies, including Agragene, are bringing biological pest control into the CRISPR era with pgSIT and other molecular tools that can specifically target the pest without killing beneficial insects, polluting the water or blanketing communities with toxic airborne chemicals. San Diego–based Synvect is applying pgSIT to disease-causing mosquitoes. Meanwhile, Oxitec, which has already successfully commercialized its “Friendly” genetic modification platform in mosquitoes, is turning its attention to crop pests.
Parental-effect gene-drive elements under partial selfing, or why do Caenorhabditis genomes have hyperdivergent regions?
33170Matthew V Rockman, Genetics, 2024-10-31 08:57:53.
Self-fertile Caenorhabditis nematodes carry a surprising number of Medea elements, alleles that act in heterozygous mothers and cause death or developmental delay in offspring that don’t inherit them. At some loci, both alleles in a cross operate as independent Medeas, affecting all the homozygous progeny of a selfing heterozygote. The genomic coincidence of Medea elements and ancient, deeply coalescing haplotypes, which pepper the otherwise homogeneous genomes of these animals, raises questions about how these apparent gene-drive elements persist for long periods of time. Here I investigate how mating system affects the evolution of Medeas, and their paternal-effect counterparts, peels. Despite an intuition that antagonistic alleles should induce balancing selection by killing homozygotes, models show that, under partial selfing, antagonistic elements experience positive frequency dependence: the common allele drives the rare one extinct, even if the rare one is more penetrant. Analytical results for the threshold frequency required for one allele to invade a population show that a very weakly penetrant allele, one whose effects would escape laboratory detection, could nevertheless prevent a much more penetrant allele from invading under high rates of selfing. Ubiquitous weak antagonistic Medeas and peels could then act as localized barriers to gene flow between populations, generating genomic islands of deep coalescence. Analysis of gene expression data, however, suggest that this cannot be the whole story. A complementary explanation is that ordinary ecological balancing selection generates ancient haplotypes on which Medeas can evolve, while high homozygosity in these selfers minimizes the role of gene drive in their evolution.
Wolbachia-based emerging strategies for control of vector-transmitted disease
32708Diego Montenegro, Gerardo Cortés-Cortés, María Guadalupe Balbuena-Alonso, et al., Acta Tropica, 260. 2024-10-22 17:28:54.
Dengue fever is a mosquito-transmitted disease of great public health importance. Dengue lacks adequate vaccine protection and insecticide-based methods of mosquito control are proving increasingly ineffective. Here we review the emerging use of mosquitoes transinfected with the obligate intracellular bacterium Wolbachia pipientis for vector control. Wolbachia often induces cytoplasmic incompatibility in its mosquito hosts, resulting in infertile progeny between an infected male and an uninfected female. Wolbachia infection also suppresses the replication of pathogens in the mosquito, a process known as “pathogen blocking”. Two strategies have emerged. The first one releases Wolbachia carriers (both male and female) to replace the wild mosquito population, a process driven by cytoplasmic incompatibility and that becomes irreversible once a threshold is reached. This suppresses disease transmission mainly by pathogen blocking and frequently requires a single intervention. The second strategy floods the field population with an exclusively male population of Wolbachia-carrying mosquitoes to generate infertile hybrid progeny. In this case, transmission suppression depends largely on decreasing the population density of mosquitoes driven by infertility and requires continued mosquito release. The efficacy of both Wolbachia-based approaches has been conclusively demonstrated by randomized and non-randomized studies of deployments across the world. However, results conducted in one setting cannot be directly or easily extrapolated to other settings because dengue incidence is highly affected by the conditions into which the mosquitoes are released. Compared to traditional vector control methods, Wolbachia-based approaches are much more environmentally friendly and can be effective in the medium/long term. On the flip side, they are much more complex and cost-intensive operations, requiring a substantial investment, infrastructure, trained personnel, coordination between agencies, and community engagement. Finally, we discuss recent evidence suggesting that the release of Wolbachia-transinfected mosquitoes has a moderate potential risk of spreading potentially dangerous genes in the environment.
Why are gene drive technologies being considered to help restore biodiversity on islands?
32530Outreach Network for Gene Drive Research, 2024-10-15 11:55:45.
Researchers have been studying how to harness gene drives to solve some of society’s most intractable problems for a long time. Public health and ecosystem conservation are two of the main areas where research has focused, although other uses are also possible.
Identification of novel genes responsible for a pollen killer present in local natural populations of Arabidopsis thaliana
32527Anthony Ricou, Matthieu Simon, et al., bioRxiv, 2024-10-15 11:51:17.
Certain genetic elements are qualified as selfish because they favor their transmission to the progeny during reproduction to the detriment of gametes that do not carry them. These elements are widespread in fungi as well as in plants or in animals, and they are made up of two or even three components, which are specific to each species. Therefore, they must be studied on a case-by-case basis. Moreover, understanding how they appear and propagate in local population remains a major issue in evolutionary biology. Here we have characterized, in the model plant Arabidopsis, the three genes involved in such an element, called a pollen killer. This pollen killer targets the mitochondria to cause the death of pollen grains that do not carry it. We investigated the three genes in several hundred genotypes collected worldwide, giving us a global view of their diversity at the species level. We also found that some French local populations contain both sensitive and killer plants, which constitutes an invaluable resource for studying the evolution of a pollen killer in the wild.
Understanding gene flow and its implications for gene drive research
31547Outreach Network for Gene Drive Research, 2024-09-16 09:02:52.
Gene flow is the transfer of genetic information from one population to another. Also known as gene transfer or gene migration, it plays a crucial role in the evolution and adaptation of species. Understanding the dynamics of gene flow is essential to assess the potential risks and benefits of gene drive approaches. Gene drive technology works by promoting the inheritance of a selected genetic trait within a population, leading to this trait becoming increasingly common within a specific species over time. Researchers have been studying how to harness this technology to address global challenges, including to control the transmission of vector-borne diseases and populations of invasive alien species which threaten sensitive ecosystems. Gene flow occurs naturally in the environment through two main dynamics: Vertical gene flow happens through mating, transferring genetic traits from one generation to another within a species or between closely related species. It is a natural part of evolutionary processes and plays a significant role in how traits are inherited. Horizontal gene flow involves the transfer of genes through non-sexual routes to unrelated organisms. While more common in bacteria, this type of gene flow is much less frequent in complex organisms. The potential implications of gene flow for gene drive research vary depending on specific circumstances. For example, gene drives could spread beneficial traits to malaria-carrying mosquitoes to help combat the disease. However, researchers must also consider whether the genetic modification could be passed on beyond its target population and, if so, whether it could lead to unintended impacts. Current studies indicate that gene flow between targeted and non-target species is generally unlikely due to genetic and ecological barriers. Despite this low probability, researchers continue to explore and refine gene drive technologies, notably by developing systems with built-in safeguards. These strategies aim to control how far and fast gene drives can spread by designing systems that only activate under specific conditions or within certain populations, or are self-limiting through time.
Is Kenya ready to turn to technology to finally defeat malaria?
31451Brygettes Ngana, Nation, 2024-09-04 21:31:11.
For decades, researchers have tested and refined dozens of methods to combat malaria, striving to outmaneuver the resilient mosquito. From deploying bed nets to developing indoor residual spraying, these strategies have formed the frontline defense against this persistent parasite. Over the years, tactics like sleeping under a treated mosquito net and destroying mosquito breeding areas have become ingrained in our daily lives. Yet, malaria remains one of the deadliest diseases in Africa, claiming nearly 600,000 lives annually, the majority of whom are children under the age of five. The disease is transmitted by the parasite Plasmodium falciparum, found in the female Anopheles mosquito, and thrive in the warm, tropical climates found across much of the continent. The World Health Organization (WHO) indicates that 249 million cases of malaria occurred in just 85 malaria-endemic countries in 2022. Nine out of 10 of these deaths occurred in Africa. Despite the development of new vaccines, and antimalarial drugs, progress in reducing malaria transmission, WHO says, has slowed. Even in some developed countries where it was once a distant memory, the disease is making a comeback.
New genetic-editing technique to alter the traits and fates of wild populations
31454Lori Dajose, CalTech, 2024-09-03 21:38:08.
Gene drives are a common technology used to insert a novel gene into a population—for example, to make mosquitos resistant to malaria. They can also be used to modify existing genes, such as making herbicide-resistant weeds susceptible to herbicides once again or even to suppress invasive populations. However, gene drives often face social concerns and regulatory challenges because they involve the spread of transgenes (genes that have been transferred and integrated into an organism's DNA) to high frequency. The new technique, called an Allele Sail, uses the CRISPR/Cas9 genome-editing technology to introduce a targeted "editor" into a population at low frequency. This editor itself does not increase in frequency as organisms reproduce, however, any organism that mates with an editor-carrying organism will become altered at the genomic position targeted by the editor, passing the altered version (called an allele) of the gene down to its own offspring. In this way, the technique mimics the natural genetic process of passing down genes and mutations, and can be used in a wider range of species than traditional gene drive approaches. "Imagine you have a big room of bouncing balls, most of them white but a few are red," says Bruce Hay, professor of biology and biological engineering. "Any time a red ball—the editor—bumps into a white ball, it turns the white ball pink—the edit. As the balls bounce around, over time, more and more of them turn pink."
Wolbachia still works when it is warm
28809McKay, A., Nature Ecology and Evolution, 8. 2024-01-16 13:59:40.
Wolbachia is a maternally inherited endosymbiotic bacterium that can impede the transmission of viruses such as dengue and Zika by some mosquito vectors to humans. Over the past decade, this self-sustaining disease-control method has been rolled out in cities of increasing size; 2023 saw the largest demonstration of efficacy to date, in Medellín, Colombia. However, two key biological mechanisms that enable Wolbachia-carrying mosquitoes to spread in a population — cytoplasmic incompatibility and maternal transmission — have been shown in laboratory conditions to decline under high temperatures. Writing in Nature Climate Change in August 2023, Vásquez and colleagues conducted computational simulations to explore whether near-future warming scenarios are likely to affect the efficacy of Wolbachia-based biocontrol. The models combine empirical estimates of thermal sensitivity for one strain of Wolbachia with projections of future average temperatures and heatwaves for Cairns, Australia and Nha Trang City, Vietnam, two locations where the intervention has been deployed. Estimates of the bacterium’s successful persistence in the mosquito population remain high under tested projections of moderate and severe average warming to 2050. However, the simulations also show reduced efficacy under more variable thermal extremes; these interventions have the potential to fail under extreme warming with long heatwave durations. We selected this paper for our Year in Review collection because it exemplifies how insect thermal biology and global change analysis can offer insights relevant to human health. Testing whether climate change influences Wolbachia-based biocontrol helps to illuminate whether the promising technology is likely to remain feasible in coming years.
Gene Drive Technology Unlocks Innovative Potential Solutions At The Intersection Of Climate Change And Public Health
28705Krystal Birungi, African Media Agency, 2023-12-12 17:23:52.
The inaugural ‘Day of Health’ at the UN Climate Conference (COP-28) highlighted the dramatic impact of climate change on health, diseases and in particular on malaria. Heads of State and climate experts converged in Dubai to emphasise the indisputable link between climate and health, echoing WHO Director-General Dr. Tedros Adhanom Ghebreyesus’s statement that climate change is a pressing public health issue. As we grapple with the harsh reality of half a million lives lost annually to malaria, including a child succumbing every minute in Africa, it is imperative to integrate innovative solutions that address both the disease and its broader public health implications exacerbated by climate change.
Incorporating ecology into gene drive modelling
28150J. Kim, K. D. Harris, I. K. Kim, S. Shemesh, P. W. Messer and G. Greenbaum, Ecology Letters, 26:S62-S80. 2023-10-23 11:37:54.
Abstract Gene drive technology, in which fast-spreading engineered drive alleles are introduced into wild populations, represents a promising new tool in the fight against vector-borne diseases, agricultural pests and invasive species. Due to the risks involved, gene drives have so far only been tested in laboratory settings while their population-level behaviour is mainly studied using mathematical and computational models. The spread of a gene drive is a rapid evolutionary process that occurs over timescales similar to many ecological processes. This can potentially generate strong eco-evolutionary feedback that could profoundly affect the dynamics and outcome of a gene drive release. We, therefore, argue for the importance of incorporating ecological features into gene drive models. We describe the key ecological features that could affect gene drive behaviour, such as population structure, life-history, environmental variation and mode of selection. We review previous gene drive modelling efforts and identify areas where further research is needed. As gene drive technology approaches the level of field experimentation, it is crucial to evaluate gene drive dynamics, potential outcomes, and risks realistically by including ecological processes.
Optimizing the delivery of self-disseminating vaccines in fluctuating wildlife populations
27639C. Schreiner, A. Basinski, C. Remien and S. Nuismer, PLOS Neglected Tropical Diseases, 17:e0011018. 2023-08-18 07:45:43.
Author summary Pathogens such as Ebola, rabies, and Lassa virus that usually infect wildlife can jump to the human population. In the worst case, this can lead to outbreaks or pandemics such as happened in 2014 with Ebola and 2019 with SARS-CoV-2. One approach to mitigate the threat of pathogens spilling into the human population is to proactively vaccinate wildlife harboring these pathogens before the pathogens infect humans. With traditional vaccines, administering enough vaccines to the wildlife population to limit pathogen spread is challenging. To address this challenge, recent technological advances have allowed the development of vaccines that allow some degree of spread of the vaccine from animal to animal. However, for a vaccination campaign using these self-disseminating vaccines to be implemented successfully, we need to know when vaccines should be administered. We used mathematical models to explore how the reservoir host’s population ecology and properties of the vaccine affect the success of a vaccination campaign. Our results demonstrate that the timing of vaccine delivery relative to seasonal reproduction can make or break the success of vaccination programs. The effectiveness of self-disseminating vaccines is optimized by introducing vaccine after the peak of seasonal reproduction when the number of animals available for vaccination is highest.
A framework for identifying fertility gene targets for mammalian pest control
25416C. C. Anna, A. Alana, E. Rey, E. Kevin, K. Sebastian, D. Ludovic, C. Jackson, E. C. Samuel, W. M. Philipp and J. G. Neil, bioRxiv, 2023.05.30.542751. 2023-06-01 07:38:46.
Fertility-targeted gene drives have been proposed as an ethical genetic approach for managing wild populations of vertebrate pests for public health and conservation benefit. This manuscript introduces a framework to identify and evaluate target gene suitability based on biological gene function, gene expression, and results from mouse knockout models. This framework identified 16 genes essential for male fertility and 12 genes important for female fertility that may be feasible targets for mammalian gene drives and other non-drive genetic pest control technology. Further, a comparative genomics analysis demonstrates the conservation of the identified genes across several globally significant invasive mammals. In addition to providing important considerations for identifying candidate genes, our framework and the genes identified in this study may have utility in developing additional pest control tools such as wildlife contraceptives.Competing Interest StatementThe authors have declared no competing interest.
Leveraging eco-evolutionary models for gene drive risk assessment
25157M. A. Combs, A. J. Golnar, J. M. Overcash, A. L. Lloyd, K. R. Hayes, D. A. O’Brochta and K. M. Pepin, Trends in Genetics, 2023-05-15 15:09:00.
As development of gene drive systems accelerates and diversifies, predicting outcomes for target populations and the potential for human and environmental risks requires accounting for numerous eco-evolutionary processes.Gene drive dynamic models quantify the influence of features across genetics (e.g., resistance development and standing genetic diversity), demographics (e.g., mating systems and inbreeding), spatial ecology (e.g., dispersal and competition), biotic and abiotic environments (e.g., climate variation and landscape structure), and implementation strategies (e.g., introduction size and timing) on gene drive outcomes.Synthesizing published gene drive models reveals research trends, knowledge gaps, and emergent principles. Modeling limitations and tradeoffs are discussed.Integrating an iterative modeling approach within the existing phased pathway for gene drive research improves utility for risk assessment.
Convention on Biological Diversity Process
34382GeneConvene Global Collaborative, 2023-04-11 13:11:27.
The image describes organizational elements and hierarchy within the United Nations system to situate the activities undertaken for the implementation of the Convention on Biological Diversity (CBD, effective Dec 1993) and its supplementary treaty the Cartagena Protocol on Biosafety to the CBD (effective Sept 2003). It also outlines the two yearly cycle of events and workflow via meetings such as the COP (Conference of the Parties) and MOP (Meeting of the Parties) organized by the CBD Secretariat to support representatives of Parties, non-Parties, non-governmental organizations and other associated organizations, and observers to discuss past work and establish future areas/programs of work related to the implementation of the treaties.
What are gene drivers and why do 300,000 people want them banned?
23828Anika, Social Bites, 2022-10-21 23:39:53.
Ecologists in Action and Madrid Agroecologico submitted 300,000 citizen signatures to the Ministry of Ecological Transition and Demographic Challenge, asking Minister Teresa Ribera to give Spain a boost. International moratorium on technology for the release of organisms modified with gene drives (OIG) It will be discussed during the negotiations of the XV Conference on the Convention on Biological Diversity to be held in December. During the delivery of the signatures, the participants risks to human health and the environment of this new gene technology. Activists claimed with a banner that this genetic engineering technology contained an international moratorium and “danger” for environmentalists.
Investigating CRISPR/Cas9 gene drive for production of disease-preventing prion gene alleles
22796A. R. Castle, S. Wohlgemuth, L. Arce and D. Westaway, PLoS One, 17:e0269342. 2022-06-07 09:14:53.
Prion diseases are a group of fatal neurodegenerative disorders that includes chronic wasting disease, which affects cervids and is highly transmissible. Given that chronic wasting disease prevalence exceeds 30% in some endemic areas of North America, and that eventual transmission to other mammalian species, potentially including humans, cannot be ruled out, novel control strategies beyond population management via hunting and/or culling must be investigated. Prion diseases depend upon post-translational conversion of the cellular prion protein, encoded by the Prnp gene, into a disease-associated conformation; ablation of cellular prion protein expression, which is generally well-tolerated, eliminates prion disease susceptibility entirely. Inspired by demonstrations of gene drive in caged mosquito species, we aimed to test whether a CRISPR/Cas9-based gene drive mechanism could, in principle, promote the spread of a null Prnp allele among mammalian populations. First, we showed that transient co-expression of Cas9 and Prnp-directed guide RNAs in RK13 cells generates indels within the Prnp open-reading frame, indicating that repair of Cas9-induced double-strand breaks by non-homologous end-joining had taken place. Second, we integrated a ~1.2 kb donor DNA sequence into the Prnp open-reading frame in N2a cells by homology-directed repair following Cas9-induced cleavages and confirmed that integration occurred precisely in most cases. Third, we demonstrated that electroporation of Cas9/guide RNA ribonucleoprotein complexes into fertilised mouse oocytes resulted in pups with a variety of disruptions to the Prnp open reading frame, with a new coisogenic line of Prnp-null mice obtained as part of this work. However, a technical challenge in obtaining expression of Cas9 in the male germline prevented implementation of a complete gene drive mechanism in mice.
Could species-focused suppression of Aedes aegypti, the yellow fever mosquito, and Aedes albopictus, the tiger mosquito, affect interacting predators? An evidence synthesis from the literature
20971J. A. S. Bonds, C. M. Collins and L.-C. Gouagna, Pest Management Science, 2022-03-16 07:20:33.
The risks of Aedes aegypti and Aedes albopictus nuisance and vector-borne diseases are rising and the adverse effects of broad-spectrum insecticide application has promoted species-specific techniques, such as sterile insect technique (SIT) and other genetic strategies, as contenders in their control operations. When specific vector suppression is proposed, potential effects on predators and wider ecosystem are some of the first stakeholder questions. These are not the only Aedes vectors of human diseases, but are those for which SIT and genetic strategies are of most interest. They vary ecologically and in habitat origin, but both have behaviourally human-adapted forms with expanding ranges. The aquatic life stages are where predation is strongest due to greater resource predictability and limited escape opportunity. These vectors' anthropic forms usually use ephemeral water bodies and man-made containers as larval habitats; predators that occur in these are mobile, opportunistic and generalist. No literature indicates that any predator depends on larvae of either species. As adults, foraging theory predicts these mosquitoes are of low profitability to predators. Energy expended hunting and consuming will mostly outweigh their energetic benefit. Moreover, as adult biomass is mobile and largely disaggregated, any predator is likely to be a generalist and opportunist. This work, which summarises much of the literature currently available on the predators of Ae. aegypti and Ae. albopictus, indicates it is highly unlikely that any predator species depends on them. Species-specific vector control to reduce nuisance and disease is thus likely to be of negligible or limited impact on non-target predators
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.
Adult mosquito predation and potential impact on the sterile insect technique
21014N. S. Bimbilé Somda, H. Maïga, W. Mamai, T. Bakhoum, T. Wallner, S. B. Poda, H. Yamada and J. Bouyer, Scientific Reports, 12:2561. 2022-02-15 06:32:02.
The sterile insect technique is a promising environmentally friendly method for mosquito control. This technique involves releasing laboratory-produced sterile males into a target field site, and its effectiveness may be affected by the extent of adult mosquito predation. Sterile males undergo several treatments. Therefore, it is vital to understand which treatments are essential in minimizing risks to predation once released. The present study investigates the predation propensity of four mantis species (Phyllocrania paradoxa, Hymenopus coronatus, Blepharopsis mendica, Deroplatys desiccata) and two gecko species (Phelsuma standingi, P. laticauda) on adult Aedes aegypti, Ae. albopictus and Anopheles arabiensis mosquitoes in a laboratory setting. First, any inherent predation preferences regarding mosquito species and sex were evaluated. Subsequently, the effects of chilling, marking, and irradiation, on predation rates were assessed. The selected predators effectively preyed on all mosquito species regardless of the treatment. Predation propensity varied over days for the same individuals and between predator individuals. Overall, there was no impact of laboratory treatments of sterile males on the relative risk of predation by the test predators, unless purposely exposed to double the required sterilizing irradiation dose. Further investigations on standardized predation trials may lead to additional quality control tools for irradiated mosquitoes.
Gene drives in malaria control: what we need to know
19289R. Mudziwapasi, M. C. Changara, A. Ndudzo, T. Kaseke, F. Godobo, F. L. Mtemeli, R. Shoko, F. Songwe, S. Ndlovu and S. Sandra Mlambo, Biotechnology and Biotechnological Equipment, 35:1623-1631. 2021-11-15 13:42:40.
Gene drives are being used to enhance a DNA sequence?s likelihood of passing between generations via sexual reproduction. Gene drives can be deployed to manipulate natural populations. They can be used to suppress populations by reducing the number of individuals in a population or to modify populations. There are more than 3000 mosquito species in the world, some of which are vectors of diseases. Malaria is a typical disease whose vectors are mosquitoes. It affects mostly tropical countries. It kills many people annually, many of whom are children. Interventions currently in use, such as indoor residual spraying and mosquito nets, are proving insufficient to eradicate malaria. Gene drives can be used in different ways to control mosquito populations or to eliminate mosquito species, thereby reducing malaria cases and deaths. This can occur through population replacement or suppression. However, before the elimination of any mosquito species for malaria control, it is necessary to consider the effects of such an action. Additionally, there is a need to review the options available for the control of mosquitoes and to create awareness of the benefits and risks of such an action. This paper, therefore, looks at the role of mosquitoes in the environment, the methods of controlling mosquitoes and malaria and necessary considerations when using gene drives inter alia.
Ecological vulnerability analysis for suppression of Drosophila suzukii by gene drives
19082C. R. Lalyer, L. Sigsgaard and B. Giese, Global Ecology and Conservation, 32:e01883. 2021-10-17 20:44:52.
Synthetic gene drives are transgenic constructs that aim to bias heredity and thereby influence the characteristics and fate of populations regarding abundance and evolution. Aside from irreversible effects in ecosystems that could be triggered by the release of a gene drive, research on confinable drives or even the reversibility of gene drives is underway and shows first success under laboratory conditions. However, their effectiveness under realistic conditions is not entirely clear unless first test releases have taken place. Since a potentially irreversible intervention into ecosystems is created, a prospective assessment is needed. We present an approach of prospective ecological vulnerability analysis for the proposed control of the invasive pest Drosophila suzukii by using gene drives. The analysis considers the accidental spread of the gene drive to the native habitat of Drosophila suzukii, with a focus on Japan. It contains a mapping of potential impacts as a consequence of the suppression of the insect. Multiple cascading effects were identified including the potential spread of the gene drive in geographic range or potential hybridization with non-target species. Determining the vulnerability of an ecosystem requires information regarding specific characteristics at different organizational levels. The vulnerability analysis of an affected ecosystem will initially serve to identify gaps in knowledge. Reducing complexity and breaking down the potential events that might arise from a gene drive population suppression enables to better understand endpoints i.e. concrete effects. Three potential effects have been selected for a specific analysis of the vulnerability of populations and species. A high vulnerability was obtained for the suppression of non-target (native) populations of Drosophila suzukii as well as for a decrease in specialized parasitoid abundance. The paper proposes the outline of a comprehensive prospective approach to understand the susceptibility of an ecosystem to unintended and irreversible harm.
Genetically Modifying Bats Could Prevent the Next Pandemic, Scientists Say
17744G. Dutton, BioSpace, 2021-07-15 13:26:12.
The next COVID pandemic could be prevented by using a gene drive to preemptively edit the genome of bats to prevent them from becoming hosts for coronaviruses, according to a proposal by scientists from Israel’s Interdisciplinary Center (IDC) Herzelia and the National Institutes of Health (NIH). Meanwhile, a team of researchers from Imperial College London is devising a way to prevent gene drives from spreading and conferring heritable, anti-competitive traits to entire populations. The two projects may be in conflict with one another, or the London project may provide a degree of safety that could manage unintended consequences. The IDC/NIH plan, Preventing COVID-59, was published recently on GitHub by Uaniv Erlich of the (IDC) and Daniel Douek of the Vaccine Research Center, National Institute of Allergies and Infectious Diseases at the NIH in the U.S. Its premise is that the SARS-CoV-2 virus – the third such virus to infect humans in the past 20 years – is part of a growing pattern of betacoronaviruses infecting human populations.
Fine-scale estimation of key life-history parameters of malaria vectors: implications for next-generation vector control technologies
17329A. L. Morris, A. Ghani and N. Ferguson, Parasites and Vectors, 14:311. 2021-06-08 14:48:41.
Mosquito control has the potential to significantly reduce malaria burden on a region, but to influence public health policy must also show cost-effectiveness. Gaps in our knowledge of mosquito population dynamics mean that mathematical modelling of vector control interventions have typically made simplifying assumptions about key aspects of mosquito ecology. Often, these assumptions can distort the predicted efficacy of vector control, particularly next-generation tools such as gene drive, which are highly sensitive to local mosquito dynamics.
GeneConvene Global Collaborative Webinar Series | Ecological Relationships of Mosquito Disease Vectors: Anticipating Risk Assessment of Gene Drive Technologies
16713Stephanie James, Hector Quemada and David O'Brochta, GeneConvene Global Collaborative, 2021-04-14 18:05:39.
An often-raised concern for the development of genetically modified mosquito technologies, particularly those involving gene drive, as tools to prevent disease transmission is the limitation of our understanding of the roles these species may play within the ecosystem. This series of webinars begins to explore what is known about the ecological relationships of mosquito vectors with regard to major types of species interactions. The speakers also will describe some of the methods by which potential interactions that may impact human or animal health and the environment can be examined in the context of case-by-case risk assessment and safety testing.
Ecological Relationships of Mosquito Disease Vectors: Anticipating Risk Assessment of Gene Drive Technologies
16707Stephanie James, Hector Quemada and David O'Brochta, GeneConvene Global Collaborative, 2021-04-14 17:54:18.
An often-raised concern for the development of genetically modified mosquito technologies, particularly those involving gene drive, as tools to prevent disease transmission is the limitation of our understanding of the roles these species may play within the ecosystem. This series of webinars begins to explore what is known about the ecological relationships of mosquito vectors with regard to major types of species interactions. The speakers also will describe some of the methods by which potential interactions that may impact human or animal health and the environment can be examined in the context of case-by-case risk assessment and safety testing.
Should we dim the sun? Will we even have a choice
16384E. Klein, New York Times, 2021-02-09 15:06:18.
“Under a White Sky” is going to be on my best books of 2021 list. It’s a wonderful work. Kolbert is the Pulitzer Prize-winning author of “The Sixth Extinction,” which you may have read. She is a staff writer at The New Yorker and just one of the great science journalists of this time, and particularly one of the great climate journalists of this age. But this book, this book’s existence is evidence of how badly that fight is going. This is a book about what we are going to need to contemplate in the coming years that we don’t want to. It’s a book about taking responsibility for how irreversibly we have altered the natural world; how often we have tried to control it, and then watched those attempts at control fail; how often the best most scientific minds of the age have come up with some brilliant solution, implemented it, and then watched calamity result. And at the same time — and this is what makes the book so worthwhile — it is a book about how there is no going back. Not now, not ever. We are in the Anthropocene. The future from here is an endless layering on of new efforts to control the consequences of our past efforts. We don’t get to flinch or pretend we don’t have to contemplate any of this. We’ve gone too far. One of the hardest things to do as a writer — and I tell you this from personal experience — is to write ambivalence. It’s easy to write a polemic or a sharp take. It is hard to write down the middle path, where you are simply describing things as they are, knowing that every possible obvious answer you can come to is probably a bad one, knowing that the hubris embedded in past attempts to solve this problem means any future brilliant idea is likely to end that way, too, but that doesn’t mean we can do nothing. But Kolbert walks that path really beautifully here, which is why I wanted to talk to her for the show. As always, my email is [email protected]. I’m always interested to know who you’d like to see on the show. The weirder, the better. So send me your guest suggestions. Here’s Elizabeth Kolbert.
Suppression gene drive in continuous space can result in unstable persistence of both drive and wild-type alleles
15938J. Champer, I. K. Kim, S. E. Champer, A. G. Clark and P. W. Messer, Mol Ecol, 2021-01-07 19:32:54.
Using spatially explicit simulations, we show that the release of a suppression drive can result in what we term "chasing" dynamics, in which wild-type individuals recolonize areas where the drive locally eliminated the population. Despite the drive subsequently reconquering these areas, complete population suppression often fails to occur or is substantially delayed. This increases the likelihood that the drive is lost or that resistance evolves. We analyze how chasing dynamics are influenced by the type of drive, its efficiency, fitness costs, and ecological factors such as the maximal growth rate of the population and levels of dispersal and inbreeding. We find that chasing is more common for lower efficiency drives when dispersal is low and that some drive mechanisms are substantially more prone to chasing behavior than others. Our results demonstrate that the population dynamics of suppression gene drives are determined by a complex interplay of genetic and ecological factors, highlighting the need for realistic spatial modeling to predict the outcome of drive releases in natural populations.
Mosquito Sexual Selection and Reproductive Control Programs
15921L. J. Cator, C. A. S. Wyer and L. C. Harrington, Trends in Parasitology, 2021-01-06 18:45:40.
Recent work has generated many key insights about specific aspects of mating behavior and physiology. Here, we synthesize these findings and classify swarming mosquito systems as polygynous. Male mating success is highly variable in swarms and evidence suggests that it is likely determined by both scramble competition between males and female choice. Incorporating this new understanding will improve both implementation and long-term stability of reproductive control tools.
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.
Invasive Species Control and Resolution of Wildlife Damage Conflicts: A Framework for Chemical and Genetically Based Management Methods
15286L. Clark, J. Eisemann, J. Godwin, K. E. Horak, K. Oh, J. O’Hare, A. Piaggio, K. Pepin and E. Ruell, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 16:52:40.
Vertebrate wildlife damage management relates to developing and employing methods to mitigate against damage caused by wildlife in the areas of food production, property damage, and animal or human health and safety. Of the many management tools available
GMOs: Implications for Biodiversity Conservation and Ecological Processes
15283Chaurasia, Anurag , Hawksworth, David L., Pessoa de Miranda, Manoela., GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 16:45:05.
This book covers a broad spectrum of topics related to GMOs and allied new gene-based technologies, biodiversity, and ecosystem processes, bringing together the contributions of researchers and regulators from around the world. The aim is to offer a clear view of the benefits and effects of genetically modified crops, insects, and other animals on the soil microbiome and ecological processes. Contributors examine issues related to the development of risk assessment procedures and regulations designed to maximize benefits while minimizing risks. Beyond the scientific challenges of GMOs, the book explores the broad and contentious terrain of ethical considerations. The contributors discuss such questions as the unintended, possibly unforeseen, consequences of releasing GMOs into ecosystems, and the likelihood that the full effects of GMOs could take years, even decades, of close monitoring to become evident. The importance of developing a precautionary approach is stressed.
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.
MGDrivE 2: A simulation framework for gene drive systems incorporating seasonality and epidemiological dynamics
14733S. L. Wu, J. B. Bennett, H. M. Sanchez C, A. J. Dolgert, T. M. Leon and J. M. Marshall, bioRxiv, 2020.10.16.343376. 2020-10-17 15:42:27.
We present MGDrivE 2 (Mosquito Gene Drive Explorer 2): an extension of and development from the MGDrivE 1 simulation framework that investigates the population dynamics of a variety of gene drive architectures and their spread through spatially-explicit mosquito populations.
Gene Drive Dynamics in Natural Populations: The Importance of Density Dependence, Space, and Sex
15277S. Dhole, A. L. Lloyd and F. Gould, Annual Review of Ecology, Evolution, and Systematics, 51:505-531. 2020-08-28 21:09:09.
The spread of synthetic gene drives is often discussed in the context of panmictic populations connected by gene flow and described with simple deterministic models. Under such assumptions, an entire species could be altered by releasing a single individual carrying an invasive gene drive, such as a standard homing drive. While this remains a theoretical possibility, gene drive spread in natural populations is more complex and merits a more realistic assessment. The fate of any gene drive released in a population would be inextricably linked to the population’s ecology. Given the uncertainty often involved in ecological assessment of natural populations, understanding the sensitivity of gene drive spread to important ecological factors is critical. Here we review how different forms of density dependence, spatial heterogeneity, and mating behaviors can impact the spread of self-sustaining gene drives. We highlight specific aspects of gene drive dynamics and the target populations that need further research.
Conservation implications of disease control
12540J. C. Buck, S. B. Weinstein, G. Titcomb and H. S. Young, Frontiers in Ecology and the Environment, 6. 2020-06-08 15:44:22.
Infectious diseases have indelibly altered human history and, in doing so, have shaped the ecology and conservation of the natural world. Attempts to control diseases often result in adverse environmental impacts, including habitat degradation and unintended outcomes such as effects on non-target species. However, in instances where the most effective strategy is to physically avoid specific species or habitats, disease can also provide critical de facto conservation benefits to organisms and ecosystems. Increasingly, new genome-editing technologies offer the potential to eradicate long-term health scourges, which disproportionately affect people in developing countries. It will be critical to incorporate an understanding of the ecological consequences of disease control - including those mediated by changes in human behavior - into management strategies, and to do so without propagating environmental injustice. In this way, scientists, resource managers, and health practitioners can help to ensure that gains for human health do not result in losses for the natural world.
Public Opinion Towards Gene Drive as a Pest Control Approach for Biodiversity Conservation and the Association of Underlying Worldviews
7348E. A. MacDonald, J. Balanovic, E. D. Edwards, W. Abrahamse, B. Frame, A. Greenaway, R. Kannemeyer, N. Kirk, F. Medvecky, T. L. Milfont, J. C. Russell and D. M. Tompkins, Environmental Communication-a Journal of Nature and Culture, 15:1-16. 2020-01-27 21:27:11.
Synthetic gene drive approaches are nascent technologies with potential applicability for pest control for conservation purposes. Responsible science mandates that society be engaged in a dialogue over new technology, particularly where there exist global ramifications as with gene drive. We hypothesize that public attitudes towards gene drive are not formed on scientific knowledge or demographics alone, but are heavily influenced by underlying worldviews, which encapsulate a broad and interactive system of attitudes, beliefs, and values. To test this, we conducted a national survey in New Zealand (n = 8199) and found that respondents clustered into four distinct segments with underlying worldviews, better able to explain attitudes toward gene drive than either the participants' scientific knowledge or other explanatory factors such demographics, political ideology or religiosity. We found that the use of gene drive for biodiversity conservation currently has moderate (32%) levels of support in New Zealand but that varied substantially across the four segments. Should gene drive become a technically viable approach for pest control, understanding the worldviews that shape public decision-making can guide a more empathetic engagement process and empower society to participate in informed decision-making about if and how gene drive should be used for conservation purposes.
Gene Drive Film
6665Save Our Seeds, 2020-01-16 16:39:24.
This is a video based on the findings in GENE DRIVES: A report on their science, applications, social aspects, ethics and regulations which you can find here. There was a Symposium on May 24, 2019 that covers the topics in the report and the presentations at that symposium can be found here.
Threshold-Dependent Gene Drives in Wild Populations – A Podcast
6900G. A. Backus and J. A. Delborne, BioScience Talks, 2019-10-08 14:04:47.
By altering the heritability of certain traits, gene drive technologies have the potential to spread desired genes through wild populations. In practice, this could lead to mosquito populations that, for example, bear traits making them resistant to the spread of malaria. Despite the huge potential for improving human well-being, concern exists that gene drives could fail in the wild or spread beyond their intended target populations. Writing in BioScience, Dr. Greg Backus, a postdoctoral researcher at the University of California, Davis, and Jason Delborne, Associate Professor of Science Policy and Society at North Carolina State University's Genetic Engineering and Society Center, describe a potential solution. Threshold-dependent gene drives could limit the spread of wild-released gene drives to target populations, increasing control and reducing the risk of unchecked spread. The authors joined us on this episode of BioScience Talks to discuss the potential of these gene drives—and also some of the questions of controllability, spread, and ecological uncertainty that relate to them. Read the article. Listen to our previous podcast on gene drives.
Genetically engineered mosquitoes out of control
4534GM Watch, GM Watch, 2019-09-11 00:00:00.
According to a new scientific publication, genetically engineered mosquitoes produced by the biotech company Oxitec (Intrexon) have escaped human control after trials in Brazil. They are now spreading in the environment. The yellow fever mosquitoes (Aedes aegypti) are genetically engineered to make it impossible for their offspring to survive. After release they were supposed to mate with female mosquitoes of the species which transmit infectious diseases, such as Dengue fever, to diminish the natural populations.
Twenty-five Years of Research Experience with the Sterile Insect Technique and Area-Wide Management of Codling Moth, Cydia pomonella (L.), in Canada
13154H. M. A. Thistlewood and G. J. R. Judd, Insects, 10:292. 2019-09-10 14:21:45.
The advent of novel genetic methods has led to renewed interest in the sterile insect technique (SIT) for management of insect pests, owing to applications in mass rearing and in the production of sterile offspring without use of irradiation. An area-wide management programme for codling moth, Cydia pomonella, has employed the SIT and other management practices over a large area (3395 to 7331 ha) of orchards and neighbouring urban, public, or First Nations lands in British Columbia, Canada, for 25 years. This project is the first to employ the SIT for C. pomonella, and the longest-running application of area-wide techniques for its control, anywhere. It was derived from basic research and applied trials from the 1960s onwards. Many biological challenges were overcome, and lessons learnt, in transferring from small- to large-scale applications of mass rearing and the SIT, with particular regard to Lepidoptera. Research has proven essential to identifying, if not resolving, issues that threaten the implementation and success of any such programme. The major challenges encountered, and the resulting research, are reviewed, as well as future directions. Recommendations are given for application of the SIT as part of any area-wide management programme for C. pomonella.
A 2017 horizon scan of emerging issues for global conservation and biological diversity
4067Sutherland, WJB, P.; Broad, S.; Clout, M.; Connor, B.; Cote, I. M.; Dicks, L. V.; Doran, H.; Entwistle, A. C.; Fleishman, E.; Fox, M.; Gaston, K. J.; Gibbons, D. W.; Jiang, Z.; Keim, B.; Lickorish, F. A.; Markillie, P.; Monk, K. A.; Pearce-Higgins, J. W.; Peck, L. S.; Pretty, J.; Spalding, M. D.; Tonneijck, F. H.; Wintle, B. C.; Ockendon, N., Trends in Ecology & Evolution, 32:31-40. 2019-09-09 00:00:00.
We present the results of our eighth annual horizon scan of emerging issues likely to affect global biological diversity, the environment, and conservation efforts in the future. The potential effects of these novel issues might not yet be fully recognized or understood by the global conservation community, and the issues can be regarded as both opportunities and risks. A diverse international team with collective expertise in horizon scanning, science communication, and conservation research, practice, and policy reviewed 100 potential issues and identified 15 that qualified as emerging, with potential substantial global effects. These issues include new developments in energy storage and fuel production, sand extraction, potential solutions to combat coral bleaching and invasive marine species, and blockchain technology.
Herbicide resistant weeds: A call to integrate conventional agricultural practices, molecular biology knowledge and new technologies
6040V. E. Perotti, A. S. Larran, V. E. Palmieri, A. K. Martinatto and H. R. Permingeat, Plant Science, 290:110255. 2019-09-06 21:01:14.
Herbicide resistant (HR) weeds are of major concern in modern agriculture. This situation is exacerbated by the massive adoption of herbicide-based technologies along with the overuse of a few active ingredients to control weeds over vast areas year after year. Also, many other anthropological, biological, and environmental factors have defined a higher rate of herbicide resistance evolution in numerous weed species around the world. This review focuses on two central points: 1) how these factors have affected the resistance evolution process; and 2) which cultural practices and new approaches would help to achieve an effective integrated weed management. We claim that global climate change is an unnoticed factor that may be acting on the selection of HR weeds, especially those evolving into non-target-site resistance mechanisms. And we present several new tools –such as Gene Drive and RNAi technologies- that may be adopted to cope with herbicide resistance spread, as well as discuss their potential application at field level. This is the first review that integrates agronomic and molecular knowledge of herbicide resistance. It covers not only the genetic basis of the most relevant resistance mechanisms but also the strengths and weaknesses of traditional and forthcoming agricultural practices.
A natural gene drive system influences bovine tuberculosis susceptibility in African buffalo: Possible implications for disease management
6038P. van Hooft, W. M. Getz, B. J. Greyling and A. D. S. Bastos, PLoS One, 14:e0221168. 2019-09-04 20:57:09.
Bovine tuberculosis (BTB) is endemic to the African buffalo (Syncerus caffer) of Hluhluwe-iMfolozi Park (HiP) and Kruger National Park, South Africa. In HiP, the disease has been actively managed since 1999 through a test-and-cull procedure targeting BTB-positive buffalo. Prior studies in Kruger showed associations between microsatellite alleles, BTB and body condition. A sex chromosomal meiotic drive, a form of natural gene drive, was hypothesized to be ultimately responsible. These associations indicate high-frequency occurrence of two types of male-deleterious alleles (or multiple-allele haplotypes). One type negatively affects body condition and BTB resistance in both sexes. The other type has sexually antagonistic effects: negative in males but positive in females. Here, we investigate whether a similar gene drive system is present in HiP buffalo, using 17 autosomal microsatellites and microsatellite-derived Y-chromosomal haplotypes from 401 individuals, culled in 2002–2004. We show that the association between autosomal microsatellite alleles and BTB susceptibility detected in Kruger, is also present in HiP. Further, Y-haplotype frequency dynamics indicated that a sex chromosomal meiotic drive also occurred in HiP. BTB was associated with negative selection of male-deleterious alleles in HiP, unlike positive selection in Kruger. Birth sex ratios were female-biased. We attribute negative selection and female-biased sex ratios in HiP to the absence of a Y-chromosomal sex-ratio distorter. This distorter has been hypothesized to contribute to positive selection of male-deleterious alleles and male-biased birth sex ratios in Kruger. As previously shown in Kruger, microsatellite alleles were only associated with male-deleterious effects in individuals born after wet pre-birth years; a phenomenon attributed to epigenetic modification. We identified two additional allele types: male-specific deleterious and beneficial alleles, with no discernible effect on females. Finally, we discuss how our findings may be used for breeding disease-free buffalo and implementing BTB test-and-cull programs.
Interpopulation spread of a parasitic B chromosome is unlikely through males in the grasshopper Eyprepocnemis plorans
6166M. I. Manrique-Poyato, J. Cabrero, M. D. López-León, F. Perfectti, R. Gómez and J. P. M. Camacho, Heredity, 124:197-206. 2019-07-08 18:29:07.
The near-neutral model of B chromosome evolution predicts that population invasion is quite fast. To test this prediction, in 1994, we introduced males of the grasshopper Eyprepocnemis plorans from a B-carrying population into a B-lacking population and monitored the evolution of B-chromosome frequency up to 2013. We observed fluctuating very low B frequency across years but, remarkably, the B chromosome introduced (the B2 variant) was found up to 1996 only, whereas the B1 variant was present from 1996 onwards, presumably introduced by fishermen using E. plorans males as bait. Effective introgression of genetic material from the donor population was evidenced by the presence of a satellite DNA on autosome 9 (up to 1999) and the presence of one individual in 2006 showing an ISSR marker profile being highly similar to that found in the donor population. This indicated that the males introduced by us effectively mated with resident females, but donor genes rapidly decreased in frequency after this non-recurrent migration event. Taken together, our results indicated: (i) that the non-recurrent migration event had a slight, transient genetic effect on the recipient population, which was diluted in only a few generations; and (ii) that even with recurrent migration (forced by fishermen) the B chromosome failed to increase in frequency. Bearing in mind that B chromosomes in this species drive through females only, we hypothesize that B chromosomes most likely failed invasion in both migration events because the migrating sex shows no B-drive.
Vereinigung Deutscher Wissenschaftler e.V. | Gene Drive Symposium-Critical Science Switzerland
6674Critical Scientists Switzerland; European Network of Scientists for Social and Environmental Responsibility; Vereinigung Deutscher Wissenschaftler, 2019-05-24 18:26:07.
Gene Drives: A report on their science, applications, social aspects, ethics and regulations
6670H. Dressel, Critical Scientists Switzerland; European Network of Scientists for Social and Environmental Responsibility; Vereinigung Deutscher Wissenschaftler, 2019-05-17 18:00:50.
Engineered Gene Drives are a new form of genetic modification that provides the tools for permanently modifying or potentially even eradicating species or populations in the wild. Unlike the previous genetically modified organisms (GMOs), gene drive organisms (GDOs) are not meant to stay where they are released, but instead are designed and purpose-built to spread and to drive their modified genes far and wide into wild populations.
Gene-drive-mediated extinction is thwarted by population structure and evolution of sib mating
11202J. J. Bull, C. H. Remien and S. M. Krone, Evolution Medicine and Public Health, 2019:66-81. 2019-05-11 14:03:57.
Genetic engineering combined with CRISPR technology has developed to the point that gene drives can, in theory, be engineered to cause extinction in countless species. Success of extinction programs now rests on the possibility of resistance evolution, which is largely unknown. Depending on the gene-drive technology, resistance may take many forms, from mutations in the nuclease target sequence (e.g. for CRISPR) to specific types of non-random population structures that limit the drive (that may block potentially any gene-drive technology).
When Policy Meets Practice: The Dilemma for Guidance on Risk Assessment Under the Cartagena Protocol on Biosafety
34344Karen E Hokanson, Frontiers in Bioengineering and Biotechnology, 7. 2019-04-30 14:52:07.
Transmission ratio distortion is frequent in Arabidopsis thaliana controlled crosses
3942Seymour, DKC, E.; Arioz, B. I.; Koenig, D.; Weigel, D., Heredity, 122:294-304. 2019-01-20 00:00:00.
The equal probability of transmission of alleles from either parent during sexual reproduction is a central tenet of genetics and evolutionary biology. Yet, there are many cases where this rule is violated. The preferential transmission of alleles or genotypes is termed transmission ratio distortion (TRD). Examples of TRD have been identified in many species, implying that they are universal, but the resolution of species-wide studies of TRD are limited. We have performed a species-wide screen for TRD in over 500 segregating F-2 populations of Arabidopsis thaliana using pooled reduced-representation genome sequencing. TRD was evident in up to a quarter of surveyed populations. Most populations exhibited distortion at only one genomic region, with some regions being repeatedly affected in multiple populations. Our results begin to elucidate the species-level architecture of biased transmission of genetic material in A. thaliana, and serve as a springboard for future studies into the biological basis of TRD in this species.
Male competition and the evolution of mating and ire-history traits in experimental populations of Aedes aegypti
3939Qureshi, AA, A.; Hollis, B.; Ponlawat, A.; Cator, L. J., Proceedings of the Royal Society B-Biological Sciences, 286:20190591. 2019-01-17 00:00:00.
Aedes aegypti is an important disease vector and a major target of reproductive control efforts. We manipulated the opportunity for sexual selection in populations of Ae. aegypti by controlling the number of males competing for a single female. Populations exposed to higher levels of male competition rapidly evolved higher male competitive mating success relative to populations evolved in the absence of competition, with an evolutionary response visible atter only five generations. We also detected correlated evolution in other important mating and life-history traits, such as acoustic signalling, fecundity and body size. Our results indicate that there is ample segregating variation for determinants of male mating competitiveness in wild populations and that increased male mating success trades-off with other important life-history traits. The mating conditions imposed on laboratory-reared mosquitoes are likely a significant determinant of male mating success in populations destined for release.
Predicting the spatial dynamics of Wolbachia infections in Aedes aegypti arbovirus vector populations in heterogeneous landscapes
3917Hancock, PAR, S. A.; Koenraadt, C. J. M.; Scott, T. W.; Hoffmann, A. A.; Godfray, H. C. J., Journal of Applied Ecology, 56:1674-1686. 2019-01-15 00:00:00.
A promising strategy for reducing the transmission of dengue and other arboviral human diseases by Aedes aegypti mosquito vector populations involves field introductions of the endosymbiotic bacteria Wolbachia. Wolbachia infections inhibit viral transmission by the mosquito, and can spread between mosquito hosts to reach high frequencies in the vector population. Wolbachia spreads by maternal transmission, and spread dynamics can be variable and highly dependent on natural mosquito population dynamics, population structure and fitness components. We develop a mathematical model of an A. aegypti metapopulation that incorporates empirically validated relationships describing density-dependent mosquito fitness components. We assume that density dependent relationships differ across subpopulations, and construct heterogeneous landscapes for which model-predicted patterns of variation in mosquito abundance and demography approximate those observed in field populations. We then simulate Wolbachia release strategies similar to that used in field trials. We show that our model can produce rates of spatial spread of Wolbachia similar to those observed following field releases. We then investigate how different types of spatio-temporal variation in mosquito habitat, as well as different fitness costs incurred by Wolbachia on the mosquito host, influence predicted spread rates. We find that fitness costs reduce spread rates more strongly when the habitat landscape varies temporally due to stochastic and seasonal processes. Synthesis and applications: Our empirically based modelling approach represents effects of environmental heterogeneity on the spatial spread of Wolbachia. The models can assist in interpreting observed spread patterns following field releases and in designing suitable release strategies for targeting spatially heterogeneous vector populations.
Population genetics of Anopheles funestus, the African malaria vector, Kenya
3936Ogola, EOO, J. O.; Mwangangi, J. M.; Masiga, D. K.; Tchouassi, D. P., Parasites & Vectors, 12:15. 2019-01-14 00:00:00.
Anopheles funestus is among the major malaria vectors in Kenya and sub-Saharan Africa and has been recently implicated in persistent malaria transmission. However, its ecology and genetic diversity remain poorly understood in Kenya.MethodsUsing 16 microsatellite loci, we examined the genetic structure of An. funestus sampled from 11 locations (n = 426 individuals) across a wide geographical range in Kenya spanning coastal, western and Rift Valley areas.ResultsKenyan An. funestus resolved as three genetically distinct clusters. The largest cluster (FUN1) broadly included samples from western and Rift Valley areas of Kenya with two clusters identified from coastal Kenya (FUN2 and FUN3), not previously reported. Geographical distance had no effect on population differentiation of An. funestus. We found a significant variation in the mean Plasmodium infectivity between the clusters ((2) = 12.1, df = 2, P = 0.002) and proportional to the malaria prevalence in the different risk zones of Kenya. Notably, there was variation in estimated effective population sizes between the clusters, suggesting possible differential impact of anti-vector interventions in represented areas.ConclusionsHeterogeneity among Kenyan populations of An. funestus will impact malaria vector control with practical implications for the development of gene-drive technologies. The difference in Plasmodium infectivity and effective population size between the clusters could suggest potential variation in phenotypic characteristics relating to competence or insecticide resistance. This is worth examining in future studies.
Spatial structure undermines parasite suppression by gene drive cargo
3896Bull, JJR, Christopher H.; Gomulkiewicz, Richard; Krone, Stephen M., PeerJ, 7:e7921. 2019-01-14 00:00:00.
Gene drives may be used in two ways to curtail vectored diseases. Both involve engineering the drive to spread in the vector population. One approach uses the drive to directly depress vector numbers, possibly to extinction. The other approach leaves intact the vector population but suppresses the disease agent during its interaction with the vector. This second application may use a drive engineered to carry a genetic cargo that blocks the disease agent. An advantage of the second application is that it is far less likely to select vector resistance to block the drive, but the disease agent may instead evolve resistance to the inhibitory cargo. However, some gene drives are expected to spread so fast and attain such high coverage in the vector population that, if the disease agent can evolve resistance only gradually, disease eradication may be feasible. Here we use simple models to show that spatial structure in the vector population can greatly facilitate persistence and evolution of resistance by the disease agent. We suggest simple approaches to avoid some types of spatial structure, but others may be intrinsic to the populations being challenged and difficult to overcome.
Modelling the potential of genetic control of malaria mosquitoes at national scale
3933North, ARB, Austin; Godfray, H. Charles J., BMC Biology, 17:26. 2019-01-11 00:00:00.
The persistence of malaria in large parts of sub-Saharan Africa has motivated the development of novel tools to complement existing control programmes, including gene-drive technologies to modify mosquito vector populations. Here, we use a stochastic simulation model to explore the potential of using a driving-Y chromosome to suppress vector populations in a 106 km2 area of West Africa including all of Burkina Faso.
Stakeholder attitudes towards the use of recombinant technology to manage the impact of an invasive species: Sea Lamprey in the North American Great Lakes
3951Thresher, REJ, M.; Drake, D. A. R., Biological Invasions, 21:575-586. 2019-01-09 00:00:00.
Several factors, including: (1) on-going difficulties of cost-effectively managing invasive species; (2) recent successes in using recombinant genetics to suppress mosquito populations; and, (3) developments in gene-drive technology, have re-invigorated interest in using genetic biotechnology to manage the impacts of invasive species. However, the extent to which there is social license' to develop and use these technologies has not been widely canvassed. We surveyed stakeholders involved directly and indirectly in managing Sea Lamprey (Petromyzon marinus) in the upper North American Great Lakes and a key community group of resource usersrecreational fishersto assess their support and concerns about researching, developing, and potentially implementing recombinant methods that an expert group assessed as likely to be effective in managing Sea Lamprey in the Great Lakes. Both groups overwhelmingly supported initiating R&D and, if risks were deemed very low, undertaking steps towards implementation. The key concern expressed by both groups was the risk of impacts to non-target taxa, including valued native populations of Sea Lamprey outside of the Great Lakes. Few respondents expressed opposition based on ethical or moral grounds, which contrasts with previous surveys on the use of recombinant technology in general. The broad support for R&D into recombinant approaches is likely to reflect trust in the nominated implementing agency (the Great Lakes Fishery Commission), its history of extensive consultation prior to undertaking management actions, and the hope that genetic biocontrol could solve the Sea Lamprey problem rather than simply managing it.
Large-cage assessment of a transgenic sex-ratio distortion strain on populations of an African malaria vector
3910Facchinelli, LN, A.; Collins, C.; Menichelli, M.; Persampieri, T.; Bucci, A.; Spaccapelo, R.; Crisanti, A.; Benedict, M., Parasites & Vectors, 12:70. 2019-01-08 00:00:00.
Novel transgenic mosquito control methods require progressively more realistic evaluation. The goal of this study was to determine the effect of a transgene that causes a male-bias sex ratio on Anopheles gambiae target populations in large insectary cages. Life history characteristics of Anopheles gambiae wild type and Ag(PMB)1 (aka (gfp)124L-2) transgenic mosquitoes, whose progeny are 95% male, were measured in order to parameterize predictive population models. Ag(PMB)1 males were then introduced at two ratios into large insectary cages containing target wild type populations with stable age distributions and densities. The predicted proportion of females and those observed in the large cages were compared. A related model was then used to predict effects of male releases on wild mosquitoes in a west African village. The frequency of transgenic mosquitoes in target populations reached an average of 0.44 +/- 0.02 and 0.56 +/- 0.02 after 6 weeks in the 1:1 and in the 3:1 release ratio treatments (transgenic male:wild male) respectively. Transgenic males caused sex-ratio distortion of 73% and 80% males in the 1:1 and 3:1 treatments, respectively. The number of eggs laid in the transgenic treatments declined as the experiment progressed, with a steeper decline in the 3:1 than in the 1:1 releases. The results of the experiment are partially consistent with predictions of the model; effect size and variability did not conform to the model in two out of three trials, effect size was over-estimated by the model and variability was greater than anticipated, possibly because of sampling effects in restocking. The model estimating the effects of hypothetical releases on the mosquito population of a West African village demonstrated that releases could significantly reduce the number of females in the wild population. The interval of releases is not expected to have a strong effect. The biological data produced to parameterize the model, the model itself, and the results of the experiments are components of a system to evaluate and predict the performance of transgenic mosquitoes. Together these suggest that the Ag(PMB)1 strain has the potential to be useful for reversible population suppression while this novel field develops.
Making a murderer: The evolutionary framing of hybrid gamete-killers
3949Sweigart, ALB, Yaniv; Fishman, Lila, Trends in Genetics, 35:245-252. 2019-01-07 00:00:00.
Recent molecular investigations of hybrid incompatibilities have revealed fascinating patterns of genetic interactions that have been interpreted as the remnants of a history of selfish evolution. Instead of framing hybrid incompatibilities in light of genetic conflict, we advocate assuming their innocence. Researchers must build a strong theory for each case, supported by population genetic evidence, such that the role of conflict in the evolution of a hybrid incompatibility can be proven beyond reasonable doubt. This will require careful investigation of the evolutionary history of these incompatibilities, a reckoning of how the reproductive biology of study organisms impacts on the likelihood of genetic conflict, and molecular evidence of the rapid selfish spread of these alleles.
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.
Alternative strategies for mosquito-borne arbovirus control
3884Achee, NLG, J. P.; Vatandoost, H.; Seixas, G.; Pinto, J.; Ching-Ng, L.; Martins, A. J.; Juntarajumnong, W.; Corbel, V.; Gouagna, C.; David, J. P.; Logan, J. G.; Orsborne, J.; Marois, E.; Devine, G. J.; Vontas, J., PLOS Neglected Tropical Diseases, 13:e0006822. 2019-01-02 00:00:00.
Mosquito-borne virusessuch as Zika, chikungunya, dengue fever, and yellow fever, among othersare of global importance. Although vaccine development for prevention of mosquito-borne arbovirus infections has been a focus, mitigation strategies continue to rely on vector control. However, vector control has failed to prevent recent epidemics and arrest expanding geographic distribution of key arboviruses, such as dengue. As a consequence, there has been increasing necessity to further optimize current strategies within integrated approaches and advance development of alternative, innovative strategies for the control of mosquito-borne arboviruses. Methods and findings This review, intended as a general overview, is one of a series being generated by the Worldwide Insecticide resistance Network (WIN). The alternative strategies discussed reflect those that are currently under evaluation for public health value by the World Health Organization (WHO) and represent strategies of focus by globally recognized public health stakeholders as potential insecticide resistance (IR)-mitigating strategies. Conditions where these alternative strategies could offer greatest public health value in consideration of mitigating IR will be dependent on the anticipated mechanism of action. Arguably, the most pressing need for endorsement of the strategies described here will be the epidemiological evidence of a public health impact. Conclusions As the burden of mosquito-borne arboviruses, predominately those transmitted by Aedes aegypti and A. albopictus, continues to grow at a global scale, new vector-control tools and integrated strategies will be required to meet public health demands. Decisions regarding implementation of alternative strategies will depend on key ecoepidemiological parameters that each is intended to optimally impact toward driving down arbovirus transmission. Author summary International public health workers are challenged by the burden of arthropod-borne viral diseases, to include mosquito-borne arboviruses transmitted by Aedes aegypti and A. albopictus due in part to lack of sustainable vector control and insecticide resistance (IR), as well as the inability to scale up and sustain existing interventions for prevention of urban epidemics. As a consequence, there has been increasing interest to advance the development of alternative methods. This review provides a general overview of alternative vector-control strategies under development for the control of arbovirus mosquito vectors and highlights how each could offer innovative public health value. Considerations to regulations, acceptance, and sustainability are also provided.
Evaluating the Probability of CRISPR-based Gene Drive Contaminating Another Species
3904Courtier-Orgogozo, VD, Antoine; Gouyon, Pierre-Henri; Boëte, Christophe, bioRxiv, 776609:27. 2019-01-02 00:00:00.
The probability D that a given CRISPR-based gene drive element contaminates another, non-target species can be estimated by the following Drive Risk Assessment Quantitative Estimate (DRAQUE) Equation: D = (hyb+transf).express.cut.flank.immune.nonextinct withhyb = probability of hybridization between the target species and a non-target speciestransf = probability of horizontal transfer of a piece of DNA containing the gene drive cassette from the target species to a non-target species (with no hybridization)express = probability that the Cas9 and guide RNA genes are expressedcut = probability that the CRISPR-guide RNA recognizes and cuts at a DNA site in the new hostflank = probability that the gene drive cassette inserts at the cut siteimmune = probability that the immune system does not reject Cas9-expressing cellsnonextinct = probability of invasion of the drive within the population We discuss and estimate each of the seven parameters of the equation, with particular emphasis on possible transfers within insects, and between rodents and humans. We conclude from current data that the probability of a gene drive cassette to contaminate another species is not insignificant. We propose strategies to reduce this risk and call for more work on estimating all the parameters of the formula.CRISPRClustered Regularly Interspaced Short Palindromic RepeatsDRAQUEDrive Risk Assessment Quantitative EstimateHGThorizontal gene transferHTThorizontal transfer of transposable elementTEtransposable element
Forcing the Farm
4558etc group, etc group, 2018-10-10 00:00:00.
This report is being issued as an alert to governments, civil society organisations and grassroots movements. It points to how gene drives, while promoted as a tool for medicine and conservation, will find their real use in food and farming by agribusiness. It calls for a pause in applied research in gene drives and a halt on releases to the environment until a thorough and public process of dialogue has taken place and rules are established that ensure clear consent and defence of food sovereignty
Editing nature: Local roots of global governance
4726Kofler, N.C., James P.; Kuzma, Jennifer; Marris, Emma; Esvelt, Kevin; Nelson, Michael Paul; Newhouse, Andrew; Rothschild, Lynn J.; Vigliotti, Vivian S.; Semenov, Misha; Jacobsen, Rowan; Dahlman, James E.; Prince, Shannon; Caccone, Adalgisa; Brown, Timothy, Science, 2018-07-05 00:00:00.
The Convention on Biological Diversity as a legal framework for safeguarding ecosystem services
34337Christian Prip, Ecosystem Services, 29:199-204. 2018-02-01 14:46:40.
Population seasonality and release timing significantly affect the probability of establishment for small releases of gene drive mosquitoes
4001Nikolov, MO, A. L.; Beaghton, A. K.; Beaghton, P. J.; Wenger, E. A.; Burt, A.; Welkhoff, P. A., American Journal of Tropical Medicine and Hygiene, 99:367-367. 2018-01-19 00:00:00.
Highly efficient CRISPR/Cas9 gene-drive systems have recently been developed, targeting reproductive-capacity and malaria-competency loci of malaria transmitting vector species, such as An. gambiae. The resulting drive systems aim to either suppress the local wild-type population or alter its genome, conveying desirable phenotypes such as P. falciparum refractoriness. The potential for sustained spread of gene drive constructs as proposed for malaria and a variety of other applications (pest control, tick borne diseases, dengue) has raised concerns for unintentional or unauthorized organism release outside approved and strictly-regulated trial sites. Previous analyses posit that as few as one or two gene drive organisms carrying efficient gene drive cassettes may establish a permanent (sub)population of genetically-modified (GM) mosquitoes with probability >50%. While these results are broad and cautionary, we show that seasonality is a fundamental environmental characteristic to consider when modeling decision variables. For the first time, we investigate the impact of gene-drive release timing and numbers on the establishment probability of GM vectors in the context of realistic seasonal population variation. We model a male sex bias, driving-Y population suppression gene drive, targeting An. gambiae, since these are among the first field trials candidate constructs. We analyze gene-drive establishment in geographies of different seasonality and spatial vector population features. We show that releasing a small number of gene-drive mosquitoes over the few weeks in the beginning of the wet season facilitates population founder effects and high establishment probability: between 60% - 80% for releases of as few as one or two mosquitoes. However, releasing genedrive mosquitoes outside this time results in much lower establishment probability, typically <20%. Our findings address crucial ethical and environmental concerns, which may guide whether, how, and where to set up gene-drive trials.
Engineered integrative and conjugative elements for efficient and inducible DNA transfer to undomesticated bacteria
3960Brophy, JANT, Alexander J.; Adams, Bryn L.; Renberg, Rebecca L.; Stratis-Cullum, Dimitra N.; Grossman, Alan D.; Voigt, Christopher A., Nature Microbiology, 3:1043-1053. 2018-01-18 00:00:00.
Engineering microorganisms to promote human or plant health will require manipulation of robust bacteria that are capable of surviving in harsh, competitive environments. Genetic engineering of undomesticated bacteria can be limited by an inability to transfer DNA into the cell. Here we developed an approach based on the integrative and conjugative element from Bacillus subtilis (ICEBs1) to overcome this problem. A donor strain (XPORT) was built to transfer miniaturized integrative and conjugative elements (mini-ICEBs1) to undomesticated bacteria. The strain was engineered to enable inducible control over conjugation, to integrate delivered DNA into the chromosome of the recipient, to restrict spread of heterologous DNA through separation of the type IV secretion system from the transferred DNA, and to enable simple isolation of engineered bacteria through a d-alanine auxotrophy. Efficient DNA transfer (10–1 to 10–7 conjugation events per donor) is demonstrated using 35 Gram-positive strains isolated from humans (skin and gut) and soil. Mini-ICEBs1 was used to rapidly characterize the performance of an isopropyl-?-d-thiogalactoside (IPTG)-inducible reporter across dozens of strains and to transfer nitrogen fixation to four Bacillus species. Finally, XPORT was introduced to soil to demonstrate DNA transfer under non-ideal conditions.
Evaluating active genetic options for the control of Sea Lampreys (Petromyzon marinus) in the Laurentian Great Lakes
4020Thresher, REJ, Michael; Drake, D. Andrew, Canadian Journal of Fisheries and Aquatic Sciences, 76:1186-1202. 2018-01-18 00:00:00.
For more than two decades the Great Lakes Fishery Commission has sought tactics to complement, and potentially replace, the use of barriers and lampricides to control Sea Lamprey in the Great Lakes, but thus far without success. This paper examines the potential of modern genetic technology to suppress these invasive populations. We identified six recombinant options that appeared to be moderately to highly feasible, most of which were judged by an expert panel as extremely low or low risk, and for which R&D was broadly supported by stakeholders. The two options judged to overall best combine high efficacy and low risks were a Mendelian “sex ratio drive” and genetically modifying a prey species as to kill or sterilize Sea Lamprey that fed on it. Core issues regarding use of genetic biocontrol in the Great Lakes include technical problems associated with maintaining a Sea Lamprey brood line, information gaps for most options, the extent of broader public support, and the extent and nature of national and international consultation required in making decisions about control options.
Identifying and detecting potentially adverse ecological outcomes associated with the release of gene-drive modified organisms
3980Hayes, KRH, G. R.; Dana, G. V.; Foster, S. D.; Ford, J. H.; Thresher, R.; Ickowicz, A.; Peel, D.; Tizard, M.; De Barro, P.; Strive, T.; Dambacher, J. M., Journal of Responsible Innovation, 5:S139-S158. 2018-01-18 00:00:00.
Synthetic gene drives could provide new solutions to a range of old problems such as controlling vector-borne diseases, agricultural pests and invasive species. In this paper, we outline methods to identify hazards and detect potentially adverse ecological outcomes at the individual (genotype, phenotype), population, community and ecosystem level, when progressing Gene Drive Modified Organisms through a phased test and release pathway. We discuss the strengths and weaknesses of checklists and structured hazard analysis techniques, identify methods to help meet some of the challenges of detecting adverse ecological outcomes in experiments and confined field trials, and discuss ways to improve the efficiency and statistical rigour of post-release monitoring strategies.
Simulating the effects of clumped egg laying on mosquito population dynamics in relation to gene-drive interventions
3999Morris, ALF, N.; Ghani, A., American Journal of Tropical Medicine and Hygiene, 99:279-280. 2018-01-17 00:00:00.
Gene-drive based vector control methods are a rapidly developing tool in the fight against malaria. They utilise highly targeted insertions of genes to express specific traits, such as biases in offspring sex ratio or inhibited vector competence, which are preferentially inherited by copying themselves between chromosomes. Although theoretically selfsustaining, most gene-drive methods are sensitive to numerous aspects of local mosquito population dynamics. Often however, due to gaps in our knowledge, mathematical modelling of gene drive systems makes highly simplifying assumptions about key aspects of mosquito ecology. There is an urgent need to better understand fine scale population processes to improve predictions of the likely impact of gene-drive releases and refine development of target product profiles. The principal drivers of local mosquitoes dynamics can be traced to the larval stages, where density-dependent mortality in larval habitats is a key regulator of local adult density. In this study, we explored these drivers by simulating non-homogenous egg-laying over time and analysing its relationship with differing functional forms of density dependence. We developed a discrete-time stochastic model of mosquito population dynamics, which incorporated the random, temporal clumping of egg laying. The model was fitted to historical longitudinal mosquito trapping data using advanced particle MCMC methods. From this we were able to better quantify the relationship between clumping of egg laying and densitydependent regulation of larval populations, and thus refine estimates of the mosquito reproduction number, Rm - a key determinant of the predicted impact of gene-drive interventions. We find incorporation of clumping of egg-laying improves model fit, and reduces estimates of Rm, thus making establishment and spread of gene-drive constructs more likely than predicted by models assuming higher Rm value.
Identifying knowledge gaps for gene drive research to control invasive animal species: The next CRISPR step
3998Moro, DB, Margaret; Kennedy, Malcolm; Campbell, Susan; Tizard, Mark, Global Ecology and Conservation, 13:e00363. 2018-01-16 00:00:00.
Invasive animals have been linked to the extinctions of native wildlife, and to significant agricultural financial losses or impacts. Current approaches to control invasive species require ongoing resources and management over large geographic scales, and often result in the short-term suppression of populations. New and innovative approaches are warranted. Recently, the RNA guided gene drive system based on CRISPR/Cas9 is being proposed as a potential gene editing tool that could be used by wildlife managers as a nonlethal addition or alternative to help reduce pest animal populations. While regulatory control and social acceptance are crucial issues that must be addressed, there is an opportunity now to identify the knowledge and research gaps that exist for some important invasive species. Here we systematically determine the knowledge gaps for pest species for which gene drives could potentially be applied. We apply a conceptual ecological risk framework within the gene drive context within an Australian environment to identify key requirements for undertaking work on seven exemplar invasive species in Australia. This framework allows an evaluation of the potential research on an invasive species of interest and within a gene drive and risk context. We consider the currently available biological, genetic and ecological information for the house mouse, European red fox, feral cat, European rabbit, cane toad, black rat and European starling to evaluate knowledge gaps and identify candidate species for future research. We discuss these findings in the context of future thematic areas of research worth pursuing in preparation for a more formal assessment of the use of gene drives as a novel strategy for the control of these and other invasive species.
Economic issues to consider for gene drives
3997Mitchell, PDB, Z.; McRoberts, N., Journal of Responsible Innovation, 5:S180-S202. 2018-01-15 00:00:00.
We examine four economic issues regarding gene drive applications made possible by gene editing technologies. First, whether gene drives are self-sustaining or self-limiting will largely determine which types of organizations have incentives to develop and deploy gene drives and greatly influence their governance and regulation. Social factors will also play key roles, particularly public perceptions, with these perceptions co-determined with regulation and governance. Second, gene drive applications will generate unintended negative social impacts that will partially offset benefits. Third, economic surplus, the traditional measure of economic benefits, incompletely captures the welfare impacts of gene drive applications. Fourth, gene drives imply dynamic nonlinearities that make identifying economic equilibria and general policy recommendations challenging. The potentially substantial benefits, coupled with the technical, social, and economic uncertainties surrounding gene drives, suggest that a responsible course of action is to move forward while maintaining regulatory flexibility and conducting research to resolve key uncertainties.
To reduce the global burden of human schistosomiasis, use ‘old fashioned’ snail control
4015Sokolow, SHW, Chelsea L.; Jones, Isabel J.; Lafferty, Kevin D.; Kuris, Armand; Hsieh, Michael H.; De Leo, Giulio A., Trends in Parasitology, 34:23-40. 2018-01-13 00:00:00.
Control strategies to reduce human schistosomiasis have evolved from ‘snail picking’ campaigns, a century ago, to modern wide-scale human treatment campaigns, or preventive chemotherapy. Unfortunately, despite the rise in preventive chemotherapy campaigns, just as many people suffer from schistosomiasis today as they did 50 years ago. Snail control can complement preventive chemotherapy by reducing the risk of transmission from snails to humans. Here, we present ideas for modernizing and scaling up snail control, including spatiotemporal targeting, environmental diagnostics, better molluscicides, new technologies (e.g., gene drive), and ‘outside the box’ strategies such as natural enemies, traps, and repellants. We conclude that, to achieve the World Health Assembly’s stated goal to eliminate schistosomiasis, it is time to give snail control another look.
Population dynamics of engineered underdominance and killer-rescue gene drives in the control of disease vectors
3974Edgington, MPA, Luke S., PLOS Computational Biology, 14:e1006059. 2018-01-12 00:00:00.
Vector-borne diseases represent a severe burden to both human and animal health worldwide. The methods currently being used to control a range of these diseases do not appear sufficient to address the issues at hand. As such, alternate methods for the control of vector-borne diseases are currently being investigated. Among the promising techniques currently being considered are a range of genetic control methods known as gene drive systems. These allow desirable genetic traits (such as a much reduced capacity for vectors to transmit viruses) to be spread through a target population; taking advantage of natural mate seeking behaviour to locate vector sub-populations that can be extremely difficult for humans to locate and reach. Here we use mathematical models (parameterised to consider mosquito populations) to demonstrate the robustness of the engineered underdominance and killer-rescue classes of gene drive to different ecological factors including birth and death rates; the number and quality of breeding sites (i.e. carrying capacity); and the strength of density-dependent competition during the larval development phase. We then go on to explore the range of potential outcomes that may result from the migration of individuals between two neighbouring populations.
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.
Invasion and migration of spatially self-limiting gene drives: A comparative analysis
3972Dhole, S.; Vella, M. R; Lloyd, A. L.; Gould, F., Evolutionary Applications, 11:794-808. 2018-01-10 00:00:00.
Recent advances in research on gene drives have produced genetic constructs that could theoretically spread a desired gene (payload) into all populations of a species, with a single release in one place. This attribute has advantages, but also comes with risks and ethical concerns. There has been a call for research on gene drive systems that are spatially and/or temporally self?limiting. Here, we use a population genetics model to compare the expected characteristics of three spatially self?limiting gene drive systems: one?locus underdominance, two?locus underdominance and daisy?chain drives. We find large differences between these gene drives in the minimum release size required for successfully driving a payload into a population. The daisy?chain system is the most efficient, requiring the smallest release, followed by the two?locus underdominance system, and then the one?locus underdominance system. However, when the target population exchanges migrants with a nontarget population, the gene drives requiring smaller releases suffer from higher risks of unintended spread. For payloads that incur relatively low fitness costs (up to 30%), a simple daisy?chain drive is practically incapable of remaining localized, even with migration rates as low as 0.5% per generation. The two?locus underdominance system can achieve localized spread under a broader range of migration rates and of payload fitness costs, while the one?locus underdominance system largely remains localized. We also find differences in the extent of population alteration and in the permanence of the alteration achieved by the three gene drives. The two?locus underdominance system does not always spread the payload to fixation, even after successful drive, while the daisy?chain system can, for a small set of parameter values, achieve a temporally limited spread of the payload. These differences could affect the suitability of each gene drive for specific applications.
The use of driving endonuclease genes to suppress mosquito vectors of malaria in temporally variable environments
3988Lambert, BN, Ace; Burt, Austin; Godfray, H. Charles J., Malaria Journal, 17:154. 2018-01-06 00:00:00.
The use of gene drive systems to manipulate populations of malaria vectors is currently being investigated as a method of malaria control. One potential system uses driving endonuclease genes (DEGs) to spread genes that impose a genetic load. Previously, models have shown that the introduction of DEG-bearing mosquitoes could suppress or even extinguish vector populations in spatially-heterogeneous environments which were constant over time. In this study, a stochastic spatially-explicit model of mosquito ecology is combined with a rainfall model which enables the generation of a variety of daily precipitation patterns. The model is then used to investigate how releases of a DEG that cause a bias in population sex ratios towards males are affected by seasonal or random rainfall patterns. The parameters of the rainfall model are then fitted using data from Bamako, Mali, and Mbita, Kenya, to evaluate release strategies in similar climatic conditions.
Modelling Allee effects in a transgenic mosquito population during range expansion
4026Walker, MB, Julie C.; Brown, Vicki; Childs, Lauren M., Journal of Biological Dynamics, 13:2-22. 2018-01-04 00:00:00.
Mosquitoes are vectors for many diseases that cause significant mortality and morbidity. As mosquito populations expand their range, they may undergo mate-finding Allee effects such that their ability to successfully reproduce becomes difficult at low population density. With new technology, creating target specific gene modification may be a viable method for mosquito population control. We develop a mathematical model to investigate the effects of releasing transgenic mosquitoes into newly established, low-density mosquito populations. Our model consists of two life stages (aquatic and adults), which are divided into three genetically distinct groups: heterogeneous and homogeneous transgenic that cause female infertility and a homogeneous wild type. We perform analytical and numerical analyses on the equilibria to determine the level of saturation needed to eliminate mosquitoes in a given area. This model demonstrates the potential for a gene drive system to reduce the spread of invading mosquito populations.
Is it time for synthetic biodiversity conservation?
4062Piaggio, AJS, G.; Seddon, P. J.; Alphey, L.; Bennett, E. L.; Carlson, R. H.; Friedman, R. M.; Kanavy, D.; Phelan, R.; Redford, K. H.; Rosales, M.; Slobodian, L.; Wheeler, K., Trends in Ecology & Evolution, 32:97-107. 2017-01-20 00:00:00.
Evidence indicates that, despite some critical successes, current conservation approaches are not slowing the overall rate of biodiversity loss. The field of synthetic biology, which is capable of altering natural genomes with extremely precise editing, might offer the potential to resolve some intractable conservation problems (e.g., invasive species or pathogens). However, it is our opinion that there has been insufficient engagement by the conservation community with practitioners of synthetic biology. We contend that rapid, large-scale engagement of these two communities is urgently needed to avoid unintended and deleterious ecological consequences. To this point we describe case studies where synthetic biology is currently being applied to conservation, and we highlight the benefits to conservation biologists from engaging with this emerging technology.
Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics
4039Eckhoff, PAW, E. A.; Godfray, H. C. J.; Burt, A., Proceedings of the National Academy of Sciences of the United States of America, 114:e255-e264. 2017-01-17 00:00:00.
The renewed effort to eliminate malaria and permanently remove its tremendous burden highlights questions of what combination of tools would be sufficient in various settings and what new tools need to be developed. Gene drive mosquitoes constitute a promising set of tools, with multiple different possible approaches including population replacement with introduced genes limiting malaria transmission, driving-Y chromosomes to collapse a mosquito population, and gene drive disrupting a fertility gene and thereby achieving population suppression or collapse. Each of these approaches has had recent success and advances under laboratory conditions, raising the urgency for understanding how each could be deployed in the real world and the potential impacts of each. New analyses are needed as existing models of gene drive primarily focus on nonseasonal or nonspatial dynamics. We use a mechanistic, spatially explicit, stochastic, individual-based mathematical model to simulate each gene drive approach in a variety of sub-Saharan African settings. Each approach exhibits a broad region of gene construct parameter space with successful elimination of malaria transmission due to the targeted vector species. The introduction of realistic seasonality in vector population dynamics facilitates gene drive success compared with nonseasonal analyses. Spatial simulations illustrate constraints on release timing, frequency, and spatial density in the most challenging settings for construct success. Within its parameter space for success, each gene drive approach provides a tool for malaria elimination unlike anything presently available. Provided potential barriers to success are surmounted, each achieves high efficacy at reducing transmission potential and lower delivery requirements in logistically challenged settings.
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.
Evolution of Resistance Against CRISPR/Cas9 Gene Drive
4070Unckless, RLC, A. G.; Messer, P. W., Genetics, 205:827-841. 2017-01-08 00:00:00.
CRISPR/Cas9 gene drive (CGD) promises to be a highly adaptable approach for spreading genetically engineered alleles throughout a species, even if those alleles impair reproductive success. CGD has been shown to be effective in laboratory crosses of insects, yet it remains unclear to what extent potential resistance mechanisms will affect the dynamics of this process in large natural populations. Here we develop a comprehensive population genetic framework for modeling CGD dynamics, which incorporates potential resistance mechanisms as well as random genetic drift. Using this framework, we calculate the probability that resistance against CGD evolves from standing genetic variation, de novo mutation of wild-type alleles, or cleavage repair by nonhomologous end joining (NHEJ)-a likely by-product of CGD itself. We show that resistance to standard CGD approaches should evolve almost inevitably in most natural populations, unless repair of CGD-induced cleavage via NHEJ can be effectively suppressed, or resistance costs are on par with those of the driver. The key factor determining the probability that resistance evolves is the overall rate at which resistance alleles arise at the population level by mutation or NHEJ. By contrast, the conversion efficiency of the driver, its fitness cost, and its introduction frequency have only minor impact. Our results shed light on strategies that could facilitate the engineering of drivers with lower resistance potential, and motivate the possibility to embrace resistance as a possible mechanism for controlling a CGD approach. This study highlights the need for careful modeling of the population dynamics of CGD prior to the actual release of a driver construct into the wild.
Towards the genetic control of invasive species
4047Harvey-Samuel, TA, T.; Alphey, L., Biological Invasions, 19:1683-1703. 2017-01-05 00:00:00.
Invasive species remain one of the greatest threats to global biodiversity. Their control would be enhanced through the development of more effective and sustainable pest management strategies. Recently, a novel form of genetic pest management (GPM) has been developed in which the mating behaviour of insect pests is exploited to introduce genetically engineered DNA sequences into wild conspecific populations. These 'transgenes' work in one or more ways to reduce the damage caused by a particular pest, for example reducing its density, or its ability to vector disease. Although currently being developed for use against economically important insect pests, these technologies would be highly appropriate for application against invasive species that threaten biodiversity. Importantly, these technologies have begun to advance in scope beyond insects to vertebrates, which include some of the world's worst invasives. Here we review the current state of this rapidly progressing field and, using an established set of eradication criteria, discuss the characteristics which make GPM technologies suitable for application against invasive pests.
The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito
4046Hammond, AMK, Kyros; Bruttini, Marco; North, Ace; Galizi, Roberto; Karlsson, Xenia; Kranjc, Nace; Carpi, Francesco M.; D’Aurizio, Romina; Crisanti, Andrea; Nolan, Tony, PLOS Genetics, 13:e1007039. 2017-01-04 00:00:00.
Gene drives are selfish genetic elements that are able to bias their own inheritance among offspring. Starting from very low frequencies they can rapidly invade a population in just a few generations, even when imposing a fitness cost. Gene drives based on the precise DNA cutting enzyme CRISPR have been shown recently to be highly efficient at copying themselves from one chromosome to the other during the process of gamete formation in mosquitoes, resulting in transmission to 99% of offspring instead of the 50% expected for a single gene copy. One proposed use for CRISPR-based gene drives is in the control of mosquitoes by designing the gene drive to target mosquito genes involved in fertility, thereby reducing their overall reproductive output and leading to population suppression. Like any intervention designed to suppress a population these gene drives are expected to select for mutations in the mosquito that are resistant to the drive and restore fertility to mosquitoes. We have analyzed the origin and selection of resistant alleles in caged populations of mosquitoes initiated with a gene drive construct targeting a female fertility gene. We find the selected alleles are in-frame insertions and deletions that are resistant to cleavage and restore female fertility. Our findings allow us to improve predictions on gene drive behaviour and to make concrete recommendations on how to improve future gene drive designs by decreasing the likelihood that they generate resistance.
Comparative analysis of regions with distorted segregation in three diploid populations of potato
4094Manrique-Carpintero, NCC, J. J.; Veilleux, R. E.; Buell, C. R.; Douches, D. S., G3-Genes Genomes Genetics, 6:2617-2628. 2016-01-12 00:00:00.
Genes associated with gametic and zygotic selection could underlie segregation distortion, observed as alterations of expected Mendelian genotypic frequencies in mapping populations. We studied highly dense genetic maps based on single nucleotide polymorphisms to elucidate the genetic nature of distorted segregation in potato. Three intra-and interspecific diploid segregating populations were used. DRH and D84 are crosses between the sequenced doubled monoploid DM 1-3 516 R44 Solanum tuberosum Group Phureja and either RH89-039-16 S. tuberosum or 84SD22, a S. tuberosum x S. chacoense hybrid. MSX902 is an interspecific cross between 84SD22 and Ber83 S. berthaultii x 2 x species mosaic. At the 0.05 significance level, 21%, 57%, and 51% of the total markers mapped in DRH, D84, and MSX902 exhibited distorted segregation, respectively. Segregation distortion regions for DRH were located on chromosomes 9 and 12; for D84 on chromosomes 2, 3, 4, 6, 7, and 8; and on chromosomes 1, 2, 7, 9, and 12 for MSX902. In general, each population had unique segregation distortion regions and directions of distortion. Interspecific crosses showed greater levels of distorted segregation and lower recombination rates as determined from the male parents. The different genomic regions where the segregation distortion regions occurred in the three populations likely reflect unique genetic combinations producing distorted segregation.
Rapid evolution of a Y-chromosome heterochromatin protein underlies sex chromosome meiotic drive
4088Helleu, QG, P. R.; Dubruille, R.; Ogereau, D.; Prud'homme, B.; Loppin, B.; Montchamp-Moreau, C., Proceedings of the National Academy of Sciences of the United States of America, 113:4110-4115. 2016-01-06 00:00:00.
Sex chromosome meiotic drive, the non-Mendelian transmission of sex chromosomes, is the expression of an intragenomic conflict that can have extreme evolutionary consequences. However, the molecular bases of such conflicts remain poorly understood. Here, we show that a young and rapidly evolving X-linked heterochromatin protein 1 (HP1) gene, HP1D2, plays a key role in the classical Paris sex-ratio (SR) meiotic drive occurring in Drosophila simulans. Driver HP1D2 alleles prevent the segregation of the Y chromatids during meiosis II, causing female-biased sex ratio in progeny. HP1D2 accumulates on the heterochromatic Y chromosome in male germ cells, strongly suggesting that it controls the segregation of sister chromatids through heterochromatin modification. We show that Paris SR drive is a consequence of dysfunctional HP1D2 alleles that fail to prepare the Y chromosome for meiosis, thus providing evidence that the rapid evolution of genes controlling the heterochromatin structure can be a significant source of intragenomic conflicts.
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.
National Academies of Science | Workshop: Science, Ethics, and Governance Considerations for Gene Drive Research – 2015
5544National Academy of Sciences Engineering Medicine, National Academy of Sciences, 2015-10-28 21:53:14.
Female house mice avoid fertilization by t haplotype incompatible males in a mate choice experiment
4122Manser, AK, B.; Lindholm, A. K., Journal of Evolutionary Biology, 28:54-64. 2015-01-20 00:00:00.
The t haplotype in house mice is a well-known selfish genetic element with detrimental, nonadditive fitness consequences to its carriers: recessive lethal mutations cause t/t homozygotes to perish in utero. Given the severe genetic incompatibility imposed by the t haplotype, we predict females to avoid fertilization by t haplotype incompatible males. Indeed, some of the strongest evidence for compatibility mate choice is related to the t haplotype in house mice. However, all previous evidence for compatibility mate choice in this system is based on olfactory preference. It is so far unknown how general these preferences are and whether they are relevant in an actual mating context. Here, we assess female compatibility mate choice related to t haplotypes in a setting that - for the first time - allowed females to directly interact and mate with males. This approach enabled us to analyse female behaviour during the testing period, and the resulting paternity success and fitness consequences of a given choice. We show that genetic incompatibilities arising from the t haplotype had severe indirect fitness consequences and t females avoided fertilization by t incompatible males. The results are inconclusive whether this avoidance of t fertilization by t females was caused by pre- or post-copulatory processes.
Centromere-associated meiotic drive and female fitness variation in Mimulus
4113Fishman, LK, J. K., Evolution, 69:1208-1218. 2015-01-11 00:00:00.
Female meiotic drive, in which chromosomal variants preferentially segregate to the egg pole during asymmetric female meiosis, is a theoretically pervasive but still mysterious form of selfish evolution. Like other selfish genetic elements, driving chromosomes may be maintained as balanced polymorphisms by pleiotropic or linked fitness costs. A centromere-associated driver (D) with a approximate to 58:42 female-specific transmission advantage occurs at intermediate frequency (32-40%) in the Iron Mountain population of the yellow monkeyflower, Mimulus guttatus. Previously determined male fertility costs are sufficient to prevent the fixation of D, but predict a higher equilibrium frequency. To better understand the dynamics and effects of D, we developed a new population genetic model and measured genotype-specific lifetime female fitness in the wild. In three of four years, and across all years, D imposed significant recessive seedset costs, most likely due to hitchhiking by deleterious mutations. With both male and female costs as measured, and 58:42 drive, our model predicts an equilibrium frequency of D (38%) very close to the observed value. Thus, D represents a rare selfish genetic element whose local population genetic dynamics have been fully parameterized, and the observation of equilibrium sets the stage for investigations of coevolution with suppressors.
Origin, evolution, and population genetics of the selfish Segregation Distorter gene duplication in European and African populations of Drosophila melanogaster
4108Brand, CLL, A. M.; Presgraves, D. C., Evolution, 69:1271-1283. 2015-01-06 00:00:00.
Meiotic drive elements are a special class of evolutionarily selfish genes that subvert Mendelian segregation to gain preferential transmission at the expense of homologous loci. Many drive elements appear to be maintained in populations as stable polymorphisms, their equilibrium frequencies determined by the balance between drive (increasing frequency) and selection (decreasing frequency). Here we show that a classic, seemingly balanced, drive system is instead characterized by frequent evolutionary turnover giving rise to dynamic, rather than stable, equilibrium frequencies. The autosomal Segregation Distorter (SD) system of the fruit fly Drosophila melanogaster is a selfish coadapted meiotic drive gene complex in which the major driver corresponds to a partial duplication of the gene Ran-GTPase activating protein (RanGAP). SD chromosomes segregate at similar, low frequencies of 1-5% in natural populations worldwide, consistent with a balanced polymorphism. Surprisingly, our population genetic analyses reveal evidence for parallel, independent selective sweeps of different SD chromosomes in populations on different continents. These findings suggest that, rather than persisting at a single stable equilibrium, SD chromosomes turn over frequently within populations.
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.
Analysis of segregation distortion and its relationship to hybrid barriers in rice
4154Reflinur, K, B.; Jang, S. M.; Chu, S. H.; Bordiya, Y.; Akter, M. B.; Lee, J.; Chin, J. H.; Koh, H. J., Rice, 7:3. 2014-01-12 00:00:00.
Segregation distortion (SD) is a frequently observed occurrence in mapping populations generated from crosses involving divergent genotypes. In the present study, ten genetic linkage maps constructed from reciprocal F-2 and BC1F1 mapping populations derived from the parents Dasanbyeo (indica) and Ilpumbyeo (japonica) were used to identify the distribution, effect, and magnitude of the genetic factors underlying the mechanisms of SD between the two subspecies. ResultsSD loci detected in the present study were affected by male function, female function, and zygotic selection. The most pronounced SD loci were mapped to chromosome 3 (transmitted through male gametes), chromosome 5 (transmitted through male gametes), and chromosome 6 (transmitted through female gametes). The level of SD in BC1F1 populations which defined by chi-square value independence multiple tests was relatively low in comparison to F-2 populations. Dasanbyeo alleles were transmitted at a higher frequency in both F-2 and BC1F1 populations, suggesting that indica alleles are strongly favored in inter-subspecific crosses in rice. SD loci in the present study corresponded to previously reported loci for reproductive barriers. In addition, new SD loci were detected on chromosomes 2 and 12. ConclusionThe identification of the distribution of SD and the effect of genetic factors causing SD in genetic mapping populations provides an opportunity to survey the whole genome for new SD loci and their relationships to reproductive barriers. This provides a basis for future research on the elucidation of the genetic mechanisms underlying SD in rice, and will be useful in molecular breeding programs.
The dynamic relationship between polyandry and selfish genetic elements
4181Wedell, N, Philosophical Transactions of the Royal Society B-Biological Sciences, 368:10. 2013-01-19 00:00:00.
Selfish genetic elements (SGEs) are ubiquitous in eukaryotes and bacteria, and make up a large part of the genome. They frequently target sperm to increase their transmission success, but these manipulations are often associated with reduced male fertility. Low fertility of SGE-carrying males is suggested to promote polyandry as a female strategy to bias paternity against male carriers. Support for this hypothesis is found in several taxa, where SGE-carrying males have reduced sperm competitive ability. In contrast, when SGEs give rise to reproductive incompatibilities between SGE-carrying males and females, polyandry is not necessarily favoured, irrespective of the detrimental impact on male fertility. This is due to the frequency-dependent nature of these incompatibilities, because they will decrease in the population as the frequency of SGEs increases. However, reduced fertility of SGE-carrying males can prevent the successful population invasion of SGEs. In addition, SGEs can directly influence male and female mating behaviour, mating rates and reproductive traits (e. g. female reproductive tract length and male sperm). This reveals a potent and dynamic interaction between SGEs and polyandry highlighting the potential to generate sexual selection and conflict, but also indicates that polyandry can promote harmony within the genome by undermining the spread of SGEs.
Spread of a new parasitic B chromosome variant is facilitated by high gene flow
4176Manrique-Poyato, MIL-L, M. D.; Cabrero, J.; Perfectti, F.; Camacho, J. P. M., PLOS One, 8:e83712. 2013-01-14 00:00:00.
The B-24 chromosome variant emerged several decades ago in a Spanish population of the grasshopper Eyprepocnemis plorans and is currently reaching adjacent populations. Here we report, for the first time, how a parasitic B chromosome (a strictly vertically transmitted parasite) expands its geographical range aided by high gene flow in the host species. For six years we analyzed B frequency in several populations to the east and west of the original population and found extensive spatial variation, but only a slight temporal trend. The highest B-24 frequency was found in its original population (Torrox) and it decreased closer to both the eastern and the western populations. The analysis of Inter Simple Sequence Repeat (ISSR) markers showed the existence of a low but significant degree of population subdivision, as well as significant isolation by distance (IBD). Pairwise N(e)m estimates suggested the existence of high gene flow between the four populations located in the Torrox area, with higher values towards the east. No significant barriers to gene flow were found among these four populations, and we conclude that high gene flow is facilitating B-24 diffusion both eastward and westward, with minor role for B-24 drive due to the arrival of drive suppressor genes which are also frequent in the donor population.
Local dynamics of a fast-evolving sex-ratio system in Drosophila simulans
4166Bastide, HG, P. R.; Ogereau, D.; Cazemajor, M.; Montchamp-Moreau, C., Molecular Ecology, 22:5352-5367. 2013-01-04 00:00:00.
By distorting Mendelian transmission to their own advantage, X-linked meiotic drive elements can rapidly spread in natural populations, generating a sex-ratio bias. One expected consequence is the triggering of a co-evolutionary arms race between the sex chromosome that carries the distorter and suppressors counteracting its effect. Such an arms race has been theoretically and experimentally established and can have many evolutionary consequences. However, its dynamics in contemporary populations is still poorly documented. Here, we investigate the fate of the young X-linked Paris driver in Drosophila simulans from sub-Saharan Africa to the Middle East. We provide the first example of the early dynamics of distorters and suppressors: we find consistent evidence that the driving chromosomes have been rising in the Middle East during the last decade. In addition, identical haplotypes are at high frequencies around the two co-evolving drive loci in remote populations, implying that the driving X chromosomes share a recent common ancestor and suggesting that East Africa could be the cradle of the Paris driver. The segmental duplication associated with drive presents an unusual structure in West Africa, which could reflect a secondary state of the driver. Together with our previous demonstration of driver decline in the Indian Ocean where suppression is complete, these data provide a unique picture of the complex dynamics of a co-evolutionary arms race currently taking place in natural populations of D.simulans.
General principles of single-construct chromosomal gene drive
4191Marshall, JMH, B. A., Evolution, 66:2150-2166. 2012-01-09 00:00:00.
Gene drive systems are genetic elements capable of spreading into a population even if they confer a fitness cost to their host. We consider a class of drive systems consisting of a chromosomally located, linked cluster of genes, the presence of which renders specific classes of offspring arising from specific parental crosses unviable. Under permissive conditions, a number of these elements are capable of distorting the offspring ratio in their favor. We use a population genetic framework to derive conditions under which these elements spread to fixation in a population or induce a population crash. Many of these systems can be engineered using combinations of toxin and antidote genes, analogous to Medea, which consists of a maternal toxin and zygotic antidote. The majority of toxinantidote drive systems require a critical frequency to be exceeded before they spread into a population. Of particular interest, a Z-linked Medea construct with a recessive antidote is expected to induce an all-male population crash for release frequencies above 50%. We suggest molecular tools that may be used to build these systems, and discuss their relevance to the control of a variety of insect pest species, including mosquito vectors of diseases such as malaria and dengue fever.
Complex genetic nature of sex-independent transmission ratio distortion in Asian rice species: the involvement of unlinked modifiers and sex-specific mechanisms
4189Koide, YS, Y.; Ikenaga, M.; Sawamura, N.; Matsubara, K.; Onishi, K.; Kanazawa, A.; Sano, Y., Heredity, 108:242-247. 2012-01-07 00:00:00.
Transmission ratio distortion (TRD), in which one allele is transmitted more frequently than the opposite allele, is presumed to act as a driving force in the emergence of a reproductive barrier. TRD acting in a sex-specific manner has been frequently observed in interspecific and intraspecific hybrids across a broad range of organisms. In contrast, sex-independent TRD (SITRD), which results from preferential transmission of one of the two alleles in the heterozygote through both sexes, has been detected in only a few plant species. We previously reported an S-6 locus-mediated SITRD, in which the S-6 allele from an Asian wild rice strain (Oryza rufipogon) was transmitted more frequently than the S-6(a) allele from an Asian cultivated rice strain (O. sativa) through both male and female gametes in heterozygous plants. Here, we report on the effect of a difference in genetic background on S-6 locus-mediated SITRD, based on the analysis using near-isogenic lines and the original wild strain as a parental strain for crossing. We found that the degree of TRD through the male gametes varied depending on the genetic background of the female (pistil) plants. Despite the occurrence of TRD through both male and female gametes, abnormality was detected in ovules, but not in pollen grains, in the heterozygote. These results suggest the involvement of unlinked modifiers and developmentally distinct, sex-specific genetic mechanisms in S-6 locus-mediated SITRD, raising the possibility that SITRD driven by a single locus may be affected by multiple genetic factors harbored in natural populations. Heredity (2012) 108, 242-247; doi:10.1038/hdy.2011.64; published online 27 July 2011
Local selection underlies the geographic distribution of sex-ratio drive in Drosophila neotestacea
4186Dyer, KA, Evolution, 66:973-984. 2012-01-04 00:00:00.
Selfish genetic elements promote their own transmission to the next generation, often at a cost to the host individual. A sex-ratio (SR) driving X chromosome prevents the maturation of Y-bearing sperm, and as a result is transmitted to 100% of the offspring, all of which are female. Because the spread of a SR chromosome can result in a female-biased population sex ratio, the ecological and evolutionary consequences of harboring this selfish element can be severe. In this study, we show that the prevalence of SR drive in Drosophila neotestacea varies between 0% and 30% among populations, and is common in the south whereas rare in the north. The prevalence of SR is not associated with the presence of suppressors of drive, geographic distance, or genetic distance based on autosomal microsatellite loci. Instead, our results indicate that ecological selection on SR drive varies among populations, as the prevalence of SR is highly correlated with climatic factors, with the severity of winter the best determinant of SR frequency. Thus, ecological and demographic factors may have significant consequences for the short and long term evolutionary dynamics of selfish elements and the manner with which they coevolve with the rest of the genome.
Rapid rise and fall of selfish sex-ratio X Chromosomes in Drosophila simulans: Spatiotemporal analysis of phenotypic and molecular data
4199Bastide, HC, M.; Ogereau, D.; Derome, N.; Hospital, F.; Montchamp-Moreau, C., Molecular Biology and Evolution, 28:2461-2470. 2011-01-17 00:00:00.
Sex-ratio drive, which has been documented in several Drosophila species, is induced by X-linked segregation distorters. Contrary to Mendel's law of independent assortment, the sex-ratio chromosome (X(SR)) is inherited by more than half the offspring of carrier males, resulting in a female-biased sex ratio. This segregation advantage allows X(SR) to spread in populations, even if it is not beneficial for the carriers. In the cosmopolitan species D. simulans, the Paris sex-ratio is caused by recently emerged selfish X(SR) chromosomes. These chromosomes have triggered an intragenomic conflict, and their propagation has been halted over a large area by the evolution of complete drive suppression. Previous molecular population genetics analyses revealed a selective sweep indicating that the invasion of X(SR) chromosomes was very recent in Madagascar (likely less than 100 years ago). Here, we show that X(SR) chromosomes are now declining at this location as well as in Mayotte and Kenya. Drive suppression is complete in the three populations, which display little genetic differentiation and share swept haplotypes, attesting to a common and very recent ancestry of the X(SR) chromosomes. Patterns of DNA sequence variation also indicate a fitness cost of the segmental duplication involved in drive. The data suggest that X(SR) chromosomes started declining first on the African continent, then in Mayotte, and finally in Madagascar and strongly support a scenario of rapid cycling of X chromosomes. Once drive suppression has evolved, standard X(ST) chromosomes locally replace costly X(SR) chromosomes in a few decades.
Selective microspore abortion correlated with aneuploidy: an indication of meiotic drive
4204Furness, CAR, P. J., Sexual Plant Reproduction, 24:1-8. 2011-01-02 00:00:00.
Selective megaspore abortion (monomegaspory) probably arose once in seed plants and occurs routinely in more than 70% of angiosperm species, representing one of the key characters of a heterosporous life history. In contrast, selective microspore abortion leading to pollen dispersal as pseudomonads (here termed monomicrospory) apparently arose at least twice independently within angiosperms, though it occurs in a limited number of taxa. Remarkably, similar examples of monomicrospory occur in members of two distantly related angiosperm families: the sedge family (Cyperaceae) and the epacrid subfamily (Styphelioideae) of the eudicot family Ericaceae. In sedges, monomicrospory is derived directly from normal tetrads, whereas epacrid pseudomonads apparently evolved via an intermediate stage, in which variable sterility occurs in a single tetrad. Our comparison of these two examples of selective microspore abortion highlights a correlation with aneuploidy, indicating that non-random chromosome segregation caused by monomicrospory could drive chromosomal mutations to rapid fixation through meiotic drive.
Multi-Locus Assortment (MLA) for transgene dispersal and elimination in mosquito populations
4230Rasgon, JL, PLOS One, 4:e5833. 2009-01-08 00:00:00.
: Replacement of wild-type mosquito populations with genetically modified versions is being explored as a potential strategy to control vector-borne diseases. Due to lower expected relative fitness of transgenic individuals, transgenes must be driven into populations for these scenarios to be successful. Several gene drive mechanisms exist in a theoretical sense but none are currently workable in mosquitoes. Even if strategies were workable, it would be very difficult to recall released transgenes in the event of unforeseen consequences. What is needed is a way to test transgenes in the field for feasibility, efficacy and safety prior to releasing an active drive mechanism. Methodology/Principal Findings: We outline a method, termed Multi-locus assortment (MLA), to spread transgenes into vector populations by the release of genetically-modified mosquitoes carrying multiple stable transgene inserts. Simulations indicate that [1] insects do not have to carry transgenes at more than 4 loci, [2] transgenes can be maintained at high levels by sequential small releases, the frequency of which depends on the construct fitness cost, and [3] in the case of unforeseen negative non-target effects, transgenes can be eliminated from the population by halting transgenic releases and/or mass releases of wild-type insects. We also discuss potential methods to create MLA mosquito strains in the laboratory. Conclusions/Significance: While not as efficient as active drive mechanisms, MLA has other advantages: [1] MLA strains can be constructed for some mosquito species with currently-available technology, [2] MLA will allow the ecological components of transgenic mosquito releases to be tested before actual gene drive mechanisms are ready to be deployed, [3] since MLA is not self-propagating, the risk of an accidental premature release into nature is minimized, and [4] in the case that active gene drive mechanisms prove impossible to develop, the MLA approach can be used as a back-up transgene dispersal mechanism for disease control efforts in some systems.
Large-scale selective sweep among Segregation Distorter chromosomes in African populations Drosophila melanogaster
4229Presgraves, DCG, P. R.; Cherukuri, A.; Lyttle, T. W., PLOS Genetics, 5:e1000463. 2009-01-07 00:00:00.
Segregation Distorter (SD) is a selfish, coadapted gene complex on chromosome 2 of Drosophila melanogaster that strongly distorts Mendelian transmission; heterozygous SD/SD(+) males sire almost exclusively SD-bearing progeny. Fifty years of genetic, molecular, and theory work have made SD one of the best-characterized meiotic drive systems, but surprisingly the details of its evolutionary origins and population dynamics remain unclear. Earlier analyses suggested that the SD system arose recently in the Mediterranean basin and then spread to a low, stable equilibrium frequency (1-5%) in most natural populations worldwide. In this report, we show, first, that SD chromosomes occur in populations in sub-Saharan Africa, the ancestral range of D. melanogaster, at a similarly low frequency (similar to 2%), providing evidence for the robustness of its equilibrium frequency but raising doubts about the Mediterranean-origins hypothesis. Second, our genetic analyses reveal two kinds of SD chromosomes in Africa: inversion-free SD chromosomes with little or no transmission advantage; and an African-endemic inversion-bearing SD chromosome, SD-Mal, with a perfect transmission advantage. Third, our population genetic analyses show that SD-Mal chromosomes swept across the African continent very recently, causing linkage disequilibrium and an absence of variability over 39% of the length of the second chromosome. Thus, despite a seemingly stable equilibrium frequency, SD chromosomes continue to evolve, to compete with one another, or evade suppressors in the genome.
The evolution of sex-independent transmission ratio distortion involving multiple allelic interactions at a single locus in rice
4240Koide, YI, M.; Sawamura, N.; Nishimoto, D.; Matsubara, K.; Onishi, K.; Kanazawa, A.; Sano, Y., Genetics, 180:409-420. 2008-01-18 00:00:00.
Transmission ratio distortion (TRD) is frequently observed in inter-and intraspecific hybrids of plants, leading to a violation of Mendelian inheritance. Sex-independent TRD (siTRD) was detected in a hybrid between Asian cultivated rice and its wild ancestor. Here we examined how siTRD is controlled by the S-6 locus via a mechanism in which the S-6 allele acts as a gamete eliminator, and both the male and female gametes possessing the opposite allele (S-6(a)) are aborted only in heterozygotes (S-6/S-6(a)). Fine mapping revealed that the S-6 locus is located neaar the centromere of chromosome 6. Tescross experiments using near-isogenic lines (NILs) carrying either the S-6 or S-6(a) alleles revealed that Asian rice strains frequently harbor an additional allele (S-6(n)) the presence of which, in heterozygotic states (S-6/S-6(n) and S-6(a)/S-6(n)), does not result in siTRD. A prominent reduction in the nucleotide diversity of S-6 or S-6(a) carries relative to that of S-6(n) carries was detected in the chromosomal region. These results suggest that the two incompatible alleles (S-6/S-6(a)) arose independently from S-6(n) and established genetically discontinuous relationships between limited constituents of the Asian rice population.
Centromere-associated female meiotic drive entails male fitness costs in Monkeyflowers
4236Fishman, LS, A., Science, 322:1559-1562. 2008-01-14 00:00:00.
Female meiotic drive, in which paired chromosomes compete for access to the egg, is a potentially powerful but rarely documented evolutionary force. In interspecific monkeyflower ( Mimulus) hybrids, a driving M. guttatus allele ( D) exhibits a 98: 2 transmission advantage via female meiosis. We show that extreme interspecific drive is most likely caused by divergence in centromere- associated repeat domains and document cytogenetic and functional polymorphism for drive within a population of M. guttatus. In conspecific crosses, D had a 58: 42 transmission advantage over nondriving alternative alleles. However, individuals homozygous for the driving allele suffered reduced pollen viability. These fitness effects and molecular population genetic data suggest that balancing selection prevents the fixation or loss of D and that selfish chromosomal transmission may affect both individual fitness and population genetic load.
Meiotic drive and sex determination: molecular and cytological mechanisms of sex ratio adjustment in birds
4246Rutkowska, JB, A. V., Philosophical Transactions of the Royal Society B-Biological Sciences, 363:1675-1686. 2008-01-04 00:00:00.
Differences in relative fitness of male and female offspring across ecological and social environments should favour the evolution of sex-determining mechanisms that enable adjustment of brood sex ratio to the context of breeding. Despite the expectation that genetic sex determination should not produce consistent bias in primary sex ratios, extensive and adaptive modifications of offspring sex ratio in relation to social and physiological conditions during reproduction are often documented. Such discordance emphasizes the need for empirical investigation of the proximate mechanisms for modifying primary sex ratios, and suggests epigenetic effects on sex-determining mechanisms as the most likely candidates. Birds, in particular, are thought to have an unusually direct opportunity to modify offspring sex ratio because avian females are heterogametic and because the sex-determining division in avian meiosis occurs prior to ovulation and fertilization. However, despite evidence of strong epigenetic effects on sex determination in pre-ovulatory avian oocytes, the mechanisms behind such effects remain elusive. Our review of molecular and cytological mechanisms of avian meiosis uncovers a multitude of potential targets for selection on biased segregation of sex chromosomes, which may reflect the diversity of mechanisms and levels on which such selection operates in birds. Our findings indicate that pronounced differences between sex chromosomes in size, shape, size of protein bodies, alignment at the meiotic plate, microtubule attachment and epigenetic markings should commonly produce biased segregation of sex chromosomes as the default state, with secondary evolution of compensatory mechanisms necessary to maintain unbiased meiosis. We suggest that it is the epigenetic effects that modify such compensatory mechanisms that enable context-dependent and precise adjustment of primary sex ratio in birds. Furthermore, we highlight the features of avian meiosis that can be influenced by maternal hormones in response to environmental stimuli and may account for the precise and adaptive patterns of offspring sex ratio adjustment observed in some species.
Viability effects and not meoitic drive cause dramatic departures from Mendelian inheritance for malic enzyme in hybrids of Tigriopus californicus populations
4258Willett, CSB, J. N., Journal of Evolutionary Biology, 20:1196-1205. 2007-01-16 00:00:00.
The genetic basis of post-zygotic reproductive isolation is beginning to be untangled in closely related species, but less is known about the genetics of reproductive isolation between divergent populations. Here, two genes encoding malic enzyme (ME) are isolated from the copepod Tigriopus californicus and their influence upon lowered viability in F-2 hybrids of genetically divergent populations is determined. Each ME gene has diverged extensively between T. californicus populations and one gene shows evidence for a recent selective sweep. Segregation patterns of genotypes for both ME genes in adult F-2 hybrids reveal dramatic departures from Mendelian inheritance, deviations that are not seen in F-2 nauplii implying that selection is acting during development based upon the genotype at these ME genes. These results imply that selection against deleterious gene combinations and not aberrant segregation (i.e. meiotic drive) is likely to lead to dramatic departures from Mendelian inheritance observed in these crosses.
Neurospora spore killers Sk-2 and Sk-3 suppress meiotic silencing by unpaired DNA
4254Raju, NBM, R. L.; Shiu, P. T., Genetics, 176:43-52. 2007-01-12 00:00:00.
In Neurosphora, crassa., pairing of homologous DNA segments is monitored during meiotic prophase I. Any genes not paired with a homolog, as well as any paired homologs of that gene, are silenced during the sexual phase by a mechanism known as meiotic silencing by unpaired DNA (MSUD). Two genes required for MSUD have been described previously: Sad-1 (Suppressor of ascus dominance), encoding an RNA-directed RNA polymerase, and sad-2, encoding a protein that controls the perinuclear localization of SAD-1. Inactivation of either sad-1 or sad-2 suppresses MSUD. We have now shown that MSUD is also suppressed by either of two Spore killer strains, Sk-2 and Sk-3. These were both known to contain a haplotype segment that behaves as a meiotic drive element in heterozygous crosses of killer X sensitive. Progeny ascospores not carrying the killer element fail to mature and are inviable. Crosses homozygous for either of the killer haplotypes suppress MSUD even though ascospores are not killed. The killer activity maps to the same 30-unit-long region within which recombination is suppressed in killer X sensitive crosses. We suggest that the region contains a suppressor of MSUD.
Cage trials using an endogenous meiotic drive gene in the mosquito Aedes aegypti to promote population replacement
4262Cha, SJM, A.; Chadee, D. D.; Severson, D. W., American Journal of Tropical Medicine and Hygiene, 74:62-68. 2006-01-20 00:00:00.
Control of arthropod-borne diseases based on population replacement with genetically modified noncompetent vectors has been proposed as a promising alternative to conventional control strategies. Due to likely fitness costs associated with vectors manipulated to carry anti-pathogen effector genes, the effector genes will need to be coupled with a strong drive system to rapidly sweep them into natural populations. Endogenous meiotic drive systems have strong and stable population replacement potential, and have previously been reported in two mosquito species: Aedes aegypti and Culex pipiens. To investigate the influence of an endogenous meiotic drive gene on Ae. aegypti population dynamics, we established three experimental population types that were initiated with 100%, 10%, and 1% male mosquitoes carrying a strong meiotic driver (T37 strain) and 100% sensitive females (RED strain), respectively. Among the 100% and 10% populations, early generations were highly male biased, which reflected the effects of the meiotic driver, and remained more than 60% male by the F-15. A genetic marker tightly linked with the meiotic driver on chromosome 1 showed strong selection for the T37 strain-specific allele. Similar but reduced effects of the meiotic driver were also observed in the 1% populations. These results suggest that release of A e. aegypti males carrying a strong meiotic driver into drive sensitive populations can be an effective tool for population replacement, and provide a foundation for additional studies including both experimental populations and simulations by mathematical modeling.
Fitness effects of X chromosome drive in the stalk-eyed fly, Cyrtodiopsis dalmanni
4271Wilkinson, GSJ, P. M.; Kelleher, E. S.; Muscedere, M. L.; Lorsong, A., Journal of Evolutionary Biology, 19:1851-1860. 2006-01-09 00:00:00.
Sex-ratio (SR) males produce predominantly female progeny because most Y chromosome sperm are rendered nonfunctional. The resulting transmission advantage of X-SR chromosomes should eventually cause population extinction unless segregation distortion is masked by suppressors or balanced by selection. By screening male stalk-eyed flies, Cyrtodiopsis dalmanni, for brood sex ratio we found unique SR alleles at three X-linked microsatellite loci and used them to determine if SR persists as a balanced polymorphism. We found that X-SR/X-ST females produced more offspring than other genotypes and that SR males had lower sperm precedence and exhibited lower fertility when mating eight females in 24 h. Adult survival was independent of SR genotype but positively correlated with eye span. We infer that the SR polymorphism is likely maintained by a combination of weak overdominance for female fecundity and frequency dependent selection acting on male fertility. Our discovery of two SR haplotypes in the same population in a 10-year period further suggests that this SR polymorphism may be evolving rapidly.
Segregation distortion in hybrids between the Bogota and USA subspecies of Drosophila pseudoobscura
4279Orr, HAI, S., Genetics, 169:671-682. 2005-01-17 00:00:00.
We show that, contrary to claims in the literature, "sterile" males resulting from the cross of the Bogota and USA subspecies of Drosophila pseudoobscura are weakly fertile. Surprisingly, these hybrid males produce almost all daughters when crossed to females of any genotype (pure Bogota, pure USA, hybrid F-1). Several lines of evidence suggest that this sex ratio distortion is caused by sex chromosome segregation distortion in hybrid males. We genetically analyze this normally cryptic segregation distortion and show that it involves several regions of the Bogota X chromosome that show strong epistatic interactions with each other. We further show that segregation distortion is normally masked within the Bogota subspecies by amosomal suppressors. Our analysis shows that the genetic basis of hybrid segregation distortion is similar to that of hybrid male sterility between the same subspecies. Indeed the severity of segregation distortion is correlated with the severity of sterility among hybrids. We discuss the possibility that hybrid sterility in this paradigmatic case of incipient speciation is caused by segregation distortion.
Meiotic drive at the Om locus in wild-derived inbred mouse strains
4277Kim, KT, S.; Howard, I. B.; Bell, T. A.; Doherty, H. E.; Ideraabdullah, F.; Detwiler, D. A.; De Villena, F. P. M., Biological Journal of the Linnean Society, 84:487-492. 2005-01-15 00:00:00.
Meiotic drive is an evolutionary force in which natural selection is uncoupled from organismal fitness. Recently, it has been proposed that meiotic drive and genetic drift represent major forces in the evolution of the mammalian karyotype. Meiotic drive involves two types of genetic elements, Responders and Distorters, the latter being required to induce transmission ratio distortion at the former. We have previously described the Om meiotic drive system in mouse chromosome 11. To investigate the natural history of this drive system we have characterized the alleles present at the distorter in wild-derived inbred strains. Our analysis of transmission of maternal alleles in both classical and wild-derived inbred strains indicated that driving alleles are found at high frequency in natural populations and that the existence of driving alleles predates the split between the Mus spicilegus and M. musculus lineages. (c) 2005 The Linnean Society of London.
A novel meiotic drive locus almost completely distorts segregation in Mimulus (monkeyflower) hybrids
4274Fishman, LW, J. H., Genetics, 169:347-353. 2005-01-12 00:00:00.
We report the discovery, mapping, and characterization of a meiotic drive locus (D) exhibiting nearly 100% nonrandom transmission in hybrids between two species of yellow monkeyflowers, outcrossing Mimulus guttatus and selfing M. nasutus. Only 1% of F-2 hybrids were M. nasutus homozygotes at the marker most tightly linked to D. We used a set of reciprocal backcrosses to distinguish among male-specific, female-specific, and zygote-specific sources of transmission ratio distortion. Transmission was severely distorted only when the heterozygous F, acted as the female parent in crosses to either parental species, ruling out pollen competition and zygote mortality as potential sources of drive. After four generations of backcrossing to M. nasutus, nearly isogenic lines were still >90% heterozygous at markers linked to D, suggesting that heterozygosity at the drive locus alone is sufficient for nonrandom transmission. A lack of dramatic female fitness costs in these lines rules out alternatives involving ovule or seed mortality and points to a truly meiotic mechanism of drive. The strength and direction of drive in this system is consistent with population genetic theory of selfish element evolution under different mating systems. These results are the first empirical demonstration of the strong female-specific drive predicted by new models of selfish centromere turnover.
The distribution of B chromosomes across species
4297Palestis, BGT, R.; Burt, A.; Jones, R. N., Cytogenetic and Genome Research, 106:151-158. 2004-01-15 00:00:00.
In this review we look at the broad picture of how B chromosomes are distributed across a wide range of species. We review recent studies of the factors associated with the presence of Bs across species, and provide new analyses with updated data and additional variables. The major obstacle facing comparative studies of B chromosome distribution is variation among species in the intensity of cytogenetic study. Because Bs are, by definition, not present in all individuals of a species, they may often be overlooked in species that are rarely studied. We give examples of corrections for differences in study effort, and show that after a variety of such corrections, strong correlations remain. Several major biological factors are associated with the presence of B chromosomes. Among flowering plants, Bs are more likely to occur in outcrossing than in inbred species, and their presence is also positively correlated with genome size and negatively with chromosome number. They are no more frequent in polyploids than in diploids, nor in species with multiple ploidies. Among mammals, Bs are more likely to occur in species with karyotypes consisting of mostly acrocentric chromosomes. We find no evidence for an association with chromosome number or genome size in mammals, although the sample for genome size is small. The associations with breeding system and acrocentric chromosomes were both predicted in advance, but those with genome size and chromosome number were discovered empirically and we can offer only tentative explanations for the very strong associations we have uncovered. Our understanding of why B chromosomes are present in some species and absent in others is still in its infancy, and we suggest several potential avenues for future research. Copyright (C) 2004 S. Karger AG, Basel.
Sperm survival in female stalk-eyed flies depends on seminal fluid and meiotic drive
4289Fry, CLW, G. S., Evolution, 58:1622-1626. 2004-01-07 00:00:00.
Sperm competition is common in many insect species; however, the mechanisms underlying differences in sperm precedence are not well understood. In the stalk-eyed fly, Cyrtodiopsis whitei (Diptera, Diopsidae), sperm precedence is influenced by the presence of sex chromosome meiotic drive. When drive-carrying males compete with non-driving males for fertilizations within a female, the number of progeny sired by drive males is significantly fewer than predicted by sperm mixing alone. Thus, drive males apparently suffer not only a reduction in the number of viable sperm produced, but also a reduction in sperm competitive ability. In this study, we manipulated the amount and source of seminal fluid and sperm received by females by interrupting copulations before sperm, but after seminal fluid, was transferred. We find that seminal fluid from another male influences the number of progeny sired by a drive-carrying male when both males mate with the same female. Sperm viability staining reveals that sperm from drive males are incapacitated by seminal fluid from other males within the female reproductive tract. These results suggest that multiple mating by females enables seminal fluid products to interact differentially with sperm and may reduce the transmission advantage of the drive chromosome.
Homing endonuclease genes: the rise and fall and rise again of a selfish element
4286Burt, AK, V., Current Opinion in Genetics & Development, 14:609-615. 2004-01-04 00:00:00.
Homing endonuclease genes (HEGs) are selfish genetic elements that spread by first cleaving chromosomes that do not contain them and then getting copied across to the broken chromosome as a byproduct of the repair process. The success of this strategy will depend on the opportunities for homing - in other words, the frequency with which HEG(+) and HEG(-) chromosomes come into contact - which varies widely among host taxa. HEGs are also unusual in that the selection pressure for endonuclease function disappears if they become fixed in a population, which makes them susceptible to degeneration and imposes a need for regular horizontal transmission between species. HEGs will be selected to reduce the harm done to the host organism, and this is expected to influence the evolution of their sequence specificity and maturase functions. HEGs may also be domesticated by their hosts, and are currently being put to human uses.
Adaptation for horizontal transfer in a homing endonuclease
4323Koufopanou, VG, M. R.; Burt, A., Molecular Biology and Evolution, 19:239-246. 2002-01-21 00:00:00.
Selfish genes of no function other than self-propagation are susceptible to degeneration if they become fixed in a population. and regular transfer to new species may be the only means for their long-term persistence. To test this idea we surveyed 24 species of yeast for VDE, a nuclear. intein-associated homing endonuclease gene (HEG) originally discovered in Saccharomyces cerevisiae. Phylogenetic analyses show that horizontal transmission has been a regular occurrence in its evolutionary history. Moreover, VDE appears to be specifically adapted for horizontal transmission. Its 31-bp recognition sequence is an unusually well-conserved region in an unusually well-conserved gene. In addition, the nine nucleotide sites most critical for homing are also unusually well conserved. Such adaptation for horizontal transmission presumably arose as a consequence of selection, both among HEGs at different locations in the genome and among variant,,, at the same location. The frequency of horizontal transmission must therefore be a key feature constraining the distribution and abundance of these genes.
Does Stellate cause meiotic drive in Drosophila melanogaster?
4320Belloni, MT, P.; Bozzetti, M. P.; Palumbo, G.; Robbins, L. G., Genetics, 161:1551-1559. 2002-01-18 00:00:00.
Drosophila melanogaster males deficient for the crystal (cry) locus of the Y chromosome that carry between 15 and 60 copies of the X-linked Stellate (Ste) gene are semisterile, have elevated levels of nondisjunction, produce distorted sperm genotype ratios (meiotic drive), and evince hyperactive transcription of Ste in the testes. Ste seems to be the active element in this system, and it has been proposed that the ancestral Ste gene was "selfish" and increased in frequency because it caused meiotic drive. This hypothetical evolutionary history is based on the idea that Ste overexpression, and not the lack of cry, causes the meiotic drive of cry(-) males. To test whether this is true, we have constructed a Ste-deleted X chromosome and examined the phenotype of Ste(-)/cry(-) males. If hyperactivity of Ste were necessary for the transmission defects seen in cry- males, cry males completely deficient for.Ste would be normal. Although it is impossible to construct a completely Ste(-) genotype, we find that Ste(-)/cry(-) males have exactly the same phenotype as Ste(+)/cry(-) males. The deletion of all X chromosome Ste copies not only does not eliminate meiotic drive and nondisjunction, but it also does not even reduce them below the levels produced when the X carries 15 copies of Ste.
Meiotic drive alters sperm competitive ability in stalk-eyed flies
4336Wilkinson, GSF, C. L., Proceedings of the Royal Society B-Biological Sciences, 268:2559-2564. 2001-01-14 00:00:00.
Meiotic drive results when sperm carrying a driving chromosome preferentially survive development. Meiotic drive should therefore influence sperm competition because drive males produce fewer sperm than non-drive males. Whether meiotic drive also influences the competitive ability of sperm after ejaculation is unknown. Here we report the results from reciprocal crosses that are designed for estimating the sperm precedence of male stalk-eyed flies (Cyrtodiopsis whitei) with or without X-linked meiotic drive. We find that nearly half of all sex-ratio males, as compared with 14 % of non-sex-ratio males, fail to produce young in a reciprocal cross. Furthermore, the proportion of progeny sired by a sex-ratio male in a female jointly inseminated by a non-sex-ratio male was less than expected from the number of sperm transferred. These effects are not due to differential sperm storage by females because, after a single mating with a sex-ratio male, all females stored sperm and because two sex-ratio males share paternity after jointly mating with a female. In addition to demonstrating a new mechanism of sperm competition, these results provide insight into the maintenance of sex-ratio polymorphisms. Sex-ratio males have less than one-half the fertility of non-sex-ratio males, as is required in order for frequency-dependent selection on males to produce a stable sex-ratio polymorphism.
Selection and segregation distortion in a sex-differentiated population
4335Weissing, FJvB, M., Theoretical Population Biology, 60:327-341. 2001-01-13 00:00:00.
We extend the classical model for selection at an autosomal locus in a sex-differentiated population to include segregation distortion. The equations remain the same, but the fitness parameters are interpreted differently and refer to alleles instead of genotypes. We derive conditions for internal and external stability of the equilibria, i.e., stability with respect to perturbations of alleles that are already present at equilibrium and stability with respect to invasion attempts by newly arising alleles. We show that, in a sex-differentiated population, external stability of an equilibrium can be judged on the basis of Shaw-Mohler criteria. Throughout, we compare the situation in populations with and without sex differentiation. Interestingly, internal stability is more difficult to achieve in a population without sex differentiation than in a population in which selection and segregation distortion are restricted to one sex. In a companion paper we show how the general results of the present paper can lead to new insights into specific systems such as the t complex of the house mouse. (C) 2001 Elsevier Science.
Sex chromosome meiotic drive
4332Jaenike, J, Annual Review of Ecology and Systematics, 32:25-49. 2001-01-10 00:00:00.
Sex chromosome drive refers to the unequal transmission of X and Y chromosomes from individuals of the heterogametic sex, resulting in biased sex ratios among progeny and within populations, The presence of driving sex chromosomes can reduce mean fitness within a population, bring about intragenomic conflict between the X chromosome, the Y, and the autosomes, and alter the intensity or mode of sexual selection within species. Sex chromosome drive, or its genetic equivalent, is known in plants, mammals. and flies. Many species harboring driving X chromosomes have evolved Y-linked and autosomal suppressors of drive. If a drive polymorphism is not stable, then driving chromosomes may spread to fixation and cause the extinction of a species. Certain characteristics of species, such as population density and female mating rate, may affect the probability of fixation of driving chromosomes. Thus, sex chromosome drive could be an agent of species-level selection.
Outcrossed sex allows a selfish gene to invade yeast populations
4329Goddard, MRG, D.; Burt, A., Proceedings of the Royal Society B-Biological Sciences, 268:2537-2542. 2001-01-07 00:00:00.
Homing endonuclease genes (HEGs) in eukaryotes are optional genes that have no obvious effect on host phenotype except for causing chromosomes not containing a cop), of the gene to be cut, thus causing them to be inherited at a greater than Mendelian rate via gene conversion. These genes are therefore expected to increase in frequency in outcrossed populations, but not in obligately selfed populations. In order to test this idea, we compared the dynamics of the VDE HEG in six replicate outcrossed and inbred populations of yeast (Saccharomyces cerevisiae). VDE increased in frequency from 0.21 to 0.55 in four outcrossed generations, but showed no change in frequency in the inbred populations. The absence of change in the inbred populations indicates that any effect of VDE on mitotic replication rates is less than 1%. The data from the outcrossed populations best fit a model in which 82% of individuals are derived from outcrossing and VDE is inherited by 74% of the meiotic products from heterozygotes (as compared with 50% for Mendelian genes), These results empirically demonstrate how a host mating system plays a key role in determining the population dynamics of a selfish gene.
A male-biased primary sex ratio and larval mortality in Eucheira socialis (Lepidoptera : Pieridae)
4363Underwood, DLAS, A. M., Evolutionary Ecology Research, 1:703-717. 1999-01-21 00:00:00.
We investigated the sex ratio and sex-biased mortality in the Mexican pierid butterfly, Eucheira socialis westwoodi. We studied two populations between 1990 and 1997 along Mexico Highway 40, which runs from Mazatlan, Sinaloa to Durango, Durango, Populations occurring between km 64 and 101 and between km 163 and 213 were designated 'eastern' and 'western', respectively We determined the primary sex ratio of egg masses from these populations in 1992, 1995, 1996 and 1997, The primary sex ratio varied from 68.0 to 75.5% male and from 63.7 to 79.3% male in the eastern and western populations, respectively. The frequency of significantly male-biased full sib groups was between 55 and 100% in the east and between 67 and 94% in the west. For all years, in both populations, the primary sex ratio was significantly different from 1:1. Lf the probability of a given zygote being male is the same across sibships, the distribution of the primary sex ratio should be binomial. For years where at least 10 egg masses were collected, the distribution of primary sex ratio was significantly different from a binomial in all years in the east and two of three years in the west. We studied larval and pupal mortality in these populations in 1990, 1991 and 1997. Larval mortality was consistently disproportionately male, varying from 83 to 100% male. Pupal mortality tended to be female-biased. The operational sex ratio varied from 65 to 71% male in the east and from 70 to 76% male in the west.
Evolution of driving X chromosomes and resistance factors in experimental populations of Drosophila simulans
4350Capillon, CA, A., Evolution, 53:506-517. 1999-01-08 00:00:00.
Sex-ratio drive is a particular case of meiotic drive, described in several Drosophila species, that causes males bearing driving X chromosome to produce a large excess of females in their progeny. In Drosophila simulans, driving X chromosomes and resistance factors located on the Y chromosome and on the autosomes have been previously reported. In this paper, we report the study of the dynamics of sex-ratio factors in experimental populations. We followed the evolution in frequency of driving X chromosomes in the absence of resistance factors and the evolution of resistance factors in the presence of driving X chromosomes. The driving X chromosome was lost, contrarily to theoretical expectations that predict its rapid invasion. Autosomal resistances increased in frequency, and resistant Y chromosomes invaded the population very quickly, as predicted by theoretical models. Fitness measurements showed that the loss of the driving X chromosome was due to a strong deleterious effect that was expressed only when distorting males were in competition with standard males. However, the spread of autosomal resistances reduced this deleterious effect. Implications for the maintenance of polymorphism in natural populations are discussed.
Meiotic drive favors Robertsonian metacentric chromosomes in the common shrew (Sorex araneus, Insectivora, Mammalia)
4380Wyttenbach, AB, P.; Hausser, J., Cytogenetics and Cell Genetics, 83:199-206. 1998-01-18 00:00:00.
Meiotic drive has attracted much interest because it concerns the robustness of Mendelian segregation and its genetic and evolutionary stability. We studied chromosomal meiotic drive in the common shrew (Sorex araneus, Insectivora, Mammalia), which exhibits one of the most remarkable chromosomal polymorphisms within mammalian species. The open question of the evolutionary success of metacentric chromosomes (Robertsonian fusions) versus acrocentrics in the common shrew prompted us to test whether a segregation distortion in favor of metacentrics is present in female and/or male meiosis. Performing crosses under controlled laboratory conditions with animals from natural populations, we found a clear trend toward a segregation distortion in favor of metacentrics during male meiosis, two chromosome combinations (gm and ji) being significantly preferred over their acrocentric homologs. Apart for one Robertsonian fusion (hi), this trend was absent in female meiosis. We propose a model based on recombination events between twin acrocentrics to explain the difference in transmission ratios of the same metacentric in different sexes and unequal drive of particular metacentrics in the same sex. Pooled data for female and male meiosis revealed a trend toward stronger segregation distortion for larger metacentrics. This is partially in agreement with the frequency of metacentrics occurring in natural populations of a chromosome race showing a high degree of chromosomal polymorphism.
Male eye span in stalk-eyed flies indicates genetic quality by meiotic drive suppression
4379Wilkinson, GSP, D. C.; Crymes, L., Nature, 391:276-279. 1998-01-17 00:00:00.
In some species, females choose mates possessing ornaments that predict offspring survival(1-5). However, sexual selection by female preference for male genetic quality(6-8) remains controversial because conventional genetic mechanisms maintain insufficient variation in male quality to account for costly preference and ornament evolution(9,10). Here we show that females prefer ornaments that indicate genetic quality generated by transmission conflict between the sex chromosomes, By comparing sex-ratio distributions in stalk-eyed fly (Cyrtodiopsis) progeny we found that female-biased sex ratios occur in species exhibiting eye-stalk sexual dimorphism(11,12) and female preferences for long eye span(13,14). Female-biased sex ratios result from meiotic drive(15), the preferential transmission of a 'selfish' X-chromosome. Artificial selection for 22 generations on male eye-stalk length in sexually dimorphic C. dalmanni produced longer eye-stalks and male-biased progeny sex ratios in replicate lines. Because male-biased progeny sex ratios occur when a drive-resistant Y chromosome pairs with a driving X chromosome(15), long eye span is genetically linked to meiotic drive: suppression. Male eye span therefore signals genetic quality by influencing the reproductive value of offspring(16).
Selected lines of Aedes aegypti with persistently distorted sex ratios
4386OwusuDaaku, KOW, R. J.; Butler, R. D., Heredity, 79:388-393. 1997-01-04 00:00:00.
A breeding scheme to isolate X chromosomes sensitive to drive by the T8 (Trinidad) Y chromosome of Aedes aegypti (the MD haplotype) is reported. Crosses with an Australian strain Th.I (Thursday Island) revealed not only sensitive and resistant X chromosomes but also some with the capacity to drive against the T8 Y chromosome. Four strains were created in which sex ratio was male-distorted (28-36 per cent female) for 10 generations, with no regression towards sexual parity. The proportion of females varied significantly between generations in each of the four strains. Further selection produced strains with normal sex ratios, capable of generating fewer than 15 per cent female on outcrossing to T8 males.
Meiotic drive in fungi: Chromosomal elements that cause fratricide and distort genetic ratios
4399Raju, NB, Journal of Genetics, 75:287-296. 1996-01-17 00:00:00.
Fungal Spore killers (Sk), studied most extensively in Neurospora and to a lesser extent in Podospora, Gibberella and Cochliobolus, cause the death of ascospores (= meiospores) that do not contain the killer (Sk(K)) element. When a Spore killer is heterozygous (Sk(K) x Sk(S)) in Neurospora, every ascus (= meiocyte) contains four normal-sized, black, viable ascospores (Sk(K)), and four ascospores that are tiny, unpigmented and unviable (Sk(S)). Killing of sensitive nuclei is expressed postmeiotically, and results in gross distortion of segregation ratios for Sk-linked genes. A sensitive nucleus that would otherwise die is rescued if a killer nucleus is also enclosed in the same ascospore. In Neurospora, Sk is centromere-linked (linkage group III), and when heterozygous, shows a recombination block in a 30-map-unit region spanning the centromere of linkage group III. There is no ascospore death or recombination block in killer x killer or sensitive x sensitive crosses. Spore killers are Fairly common in Gibberella fujikuroi and Neurospora sitophila but extremely rare in N. intermedia, and have not yet been found among natural isolates of N. crassa.
The effect of B chromosomes on mating success of the grasshopper Eyprepocnemis plorans
4397Martin, SA, P.; HenriquesGil, N., Genetica, 97:197-203. 1996-01-15 00:00:00.
The mating ability of E. plorans was tested in laboratory conditions in six experimental units composed of ten males and fifteen females during 31 days. When significant differences were found (three from the six cages, and in totals) they involved a decrease of matings involving males with B chromosomes. The same tendency seems to exist in females, but to a lesser extent, so that a significant effect is only detected when the totals are considered. Accessory chromosomes also delay, in both sexes, the occurrence of the first mating. No mating preferences depending on the number of Bs were detected.
A Guide to the Convention on Biological Diversity
34339Glowka, L, et al., IUCN, 1994-06-15 14:49:18.
The paternal-sex-ratio chromosome of Nasonia
4457Werren, JH, American Naturalist, 137:392-402. 1991-01-15 00:00:00.
Paternal sex ratio (PSR) is a supernumerary chromosome that is transmitted through sperm to fertilized eggs and then gains a transmission advantage by causing supercondensation of the paternal chromosomes (except itself). Because of haplodiploidy, this converts diploid females into haploid (PSR) males. PSR gains a transmission advantage because the unpaired chromosome has a higher frequency of transmission through male (mitotic) gametngenesis than through female (meiotic) gametogenesis. PSR increases in panmictic populations that produce more than 50% fertilized eggs. PSR frequency is typically reduced by population subdivision because of increased local competition among PSR males and reduced availability of females resulting from PSR action. Genetic and molecular studies of PSR have recently begun. PSR is highly heterochromatic and contains large tandem arrays of repetitive DNA unique to it. PSR apparently acts by "imprinting" the set of paternal chromosomes, resulting in their supercondensation during mitosis. Deletion studies are under way to characterize the genetic basis of PSR action and "protection" from its own action.
Sex ratio polymorphism in Drosophila pseudoobscura
4436Beckenbach, AT, American Naturalist, 137:340-343. 1991-01-14 00:00:00.
I studied "sex-ratio" (SR) genotype frequencies in two populations of Drosophila pseudoobscura from southeastern Arizona: Bear Creek Canyon and Tucson. Wild-inseminated females were collected, their fecundities measured in the laboratory, and their SR genotypes inferred by cytological analysis of their progenies. A statistically significant fecundity deficiency was observed among SR/SR females from Bear Creek Canyon. The SR frequency in the Tucson population increased at a rate consistent with the operation of meiotic drive unopposed by selection.
Expression of meiotic drive elements Spore Killer-2 and Spore Killer-3 in asci of Neurospora tetrasperma
4454Raju, NBP, D. D., Genetics, 129:25-37. 1991-01-12 00:00:00.
It was shown previously that when a chromosomal Spore killer factor is heterozygous in Neurospora species with eight-spored asci, the four sensitive ascospores in each ascus die and the four survivors are all killers. Sk-2K and Sk-3K are nonrecombining haplotypes that segregate with the centromere of linkage group III. No killing occurs when either one of these killers is homozygous, but each is sensitive to killing by the other in crosses of Sk-2K x Sk-3K. In the present study, Sk-2K and Sk-3K were transferred by recurrent backcrosses from the eight-spored species Neurospora crassa into Neurospora tetrasperma, a pseudohomothallic species which normally makes asci with four large spores, each heterokaryotic for mating type and for any other centromere-linked genes that are heterozygous in the cross. The action of Sk-2K and Sk-3K in N. tetrasperma is that predicted from their behavior in eight-spored species. A sensitive nucleus is protected from killing if it is enclosed in the same ascospore with a killer nucleus. Crosses of Sk-2K x Sk-2S, Sk-3K x Sk-3S, and Sk-2K X Sk-3K all produce four-spored asci that are wild type in appearance, with the ascospores heterokaryotic and viable. The Eight-spore gene E, which shows variable penetrance, was used to obtain N. tetrasperma asci in which two to eight spores are small and homokaryotic. When killer and sensitive alleles are segregating in the presence of E, only those ascospores that contain a killer allele survive. Half of the small ascospores are killed. In crosses of Sk-2K x Sk-3K (with E heterozygous), effectively all small ascospores are killed. The ability of N. tetrasperma to carry killer elements in cryptic condition suggests a possible role for Spore killers in the origin of pseudohomothallism, with adoption of the four-spored mode restoring ascospore viability of crosses in which killing would otherwise occur.
Sex-ratio meiotic drive in Drosophila testacea
4462James, ACJ, J., Genetics, 126:651-656. 1990-01-20 00:00:00.
We document the occurrence of "sex ratio" meiotic drive in natural populations of Drosophila testacea. "Sex ratio" males sire greater than 95% female offspring. Genetic analysis reveals that this effect is due to a meiotically driven X chromosome, as in other species of Drosophila in which "sex ratio" has been found. In contrast to other drosophilids, the "sex ratio" and standard chromosomes of D. testacea do not differ in gene arrangement, implying that the effect may be due to a single genetic factor in this species. In all likelihood, the "sex ratio" condition has evolved independently in D. testacea and in the Drosophila obscura species group, as the loci responsible for the effect occur on different chromosomal elements. An important ecological consequence of "sex ratio" is that natural populations of D. testacea exhibit a strong female bias. Because D. testacea mates, oviposits, and feeds as adults and larvae on mushrooms, this species provides an excellent opportunity to study the selective factors in nature that prevent "sex ratio" chromosomes from increasing to fixation and causing the extinction of the species.
Genetics-driving genes and chromosomes
4463Charlesworth, B, Nature, 332:394-395. 1988-01-21 00:00:00.
Thereare several genetic and chromosomal systems in which Mendel's first law - the equal probability of transmission of maternal and paternal alternative alleles or homologues - is violated. This phenomenon was named 'meiotic drive' in 1957 by Sandler and Novitski, who drew attention to the fact that it operates as an evolutionary force which can cause an increase in the population frequency of the allele or chromosome which is favoured in transmission, even if it confers a disadvantage on its carriers in terms of fitness at the level of the individual
Polymorphism in the rates of meiotic drive acting on the B-chromosome of Myrmeleotettix maculatus
4472Shaw, MWH, G. M.; Anderson, D. A., Heredity, 55:61-68. 1985-01-10 00:00:00.
A survey of all the available data on meiotic transmission rates in M. maculatus suggests that a polymorphism in female transmission rate exists in most natural populations. Differences in the frequency of the types or in the transmission rates they manifest may exist between populations or over time, but the evidence is not compelling. The data on males are also equivocal, especially because the environment may affect male transmission rate. We suggest that the polymorphism in female rates may demonstrate the selective equilibrium between the B and the genome in which it exists.
Transporting marker gene re (red eye) into a laboratory cage population of Aedes aegypti (Diptera Culicidae), using meiotic drive at MD locus
4486Wood, RJC, L. M.; Hamilton, A.; Whitelaw, A., Journal of Medical Entomology, 14:461-464. 1978-01-04 00:00:00.
An attempt has.been made to use the meiotic drive gene MD to transport a marker re (red eye) into a laboaratory population of the mosquito Aedes aegypti. The experiment produced an increase in re frequency, but also indicated that this gene has unexpectedly high fitness in the laboratory. The need for field estimates of fitness is indicated.
Experimental population-genetics of meiotic drive systems .1: Pseudo-Y chromosomal drive as a means of eliminating cage populations of Drosophila melanogaster
4487Lyttle, TW, Genetics, 86:413-445. 1977-01-05 00:00:00.
The experimental population genetics of Y-chromosome drive in Drosophila; melanogasier is approximated by studying the behavior of T(Y;S),SD lines.; These exhibit “pseudo-Y” drive through the effective coupling of the Y chromosome; to the second chromosome meiotic drive locus, Segregation distorter; (SD). T(Y;S),SD males consequently produce only male offspring. When; such lines are allowed to compete against structurally normal SD+ flies in; population cages, T(Y;S),SD males increase in frequency according to the; dynamics of a simple haploid selection model until the cage population is; eliminated as a result of a deficiency in the number of adult females. Cage; population extinction generally occurs within about seven generatiomSeveral; conclusions can be drawn from these competition cage studies:; (1) Fitness estimates for the T(Y;Z),SD lines (relative to SD+) are generally; in the range of 2-4, and these values are corroborated by; independent estimates derived from studies of migration-selection; equilibrium.; (2) Fitness estimates are unaffected by cage replication, sample time, or; the starting frequency of T(Y;Z),SD males, indicating that data from; diverse cages can be legitimately pooled to give an overall fitness; estimate.; (3) Partitioning of the T(Y;S),SD fitnesses into components of viability,; fertility, and frequency of alternate segregation (Y + SD from; X+SD+) suggests that most of the T(Y;S),SD advantage derives; from the latter two components. Improvements in the system might; involve increasing both the viability and the alternate segregation to; increase the total fitness.; While pseudo-Y drive operates quite effectively against laboratory stocks,; it is less successful in eliminating wild-type populations which are already; segregating for suppressors of SD action. This observation suggests that further
Field trial of competitive displacement of Aedes-polynesiensis by Aedes-albopictus on a Pacific atoll
6235L. Rosen, L. E. Rozeboom, W. C. Reeves, J. Saugrain and D. J. Gubler, American Journal of Tropical Medicine and Hygiene, 25:906-913. 1976-11-01 21:53:54.
Prior laboratory studies and field observations suggested that it might be possible to reduce the size of the population of, or eliminate, Aedes polynesiensis by the introduction of Aedes albopictus. The former mosquito is the principal vector of nonperiodic filariasis caused by Wuchereria bancrofti and the latter is a closely related species refractory to the development of human filariae. The practicability of such competitive displacement was studied by a field trial on a remote coral atoll where there was an established population of A. polynesiensis. Three strains of A. albopictus were liberated at separate localities on the atoll and their fate was followed for 4 years. One strain disappeared within 12 months after release and the other two disappeared within 48 months. It was not clear whether A. albopictus failed to become established because the strains were unsuitable, the general environment was inappropriate, or A. polynesiensis was present in such numbers that A. albopictus rarely succeeded in mating with its own species.
Sex-ration, meiotic drive, and group selectin in Drosophila pseudoobscura
4498Policansky, D, American Naturalist, 108:75-90. 1974-01-16 00:00:00.
Sex ratio (SR) is a widespread genetic condition of the X-chromosome in Drosophila species which causes males to produce progenies consisting almost entirely of females. Results of samples from natural populations of Drosophila pseudoobscura and results of some laboratory experiments indicate that SR males produce only about half as many sperm as normal (ST) males; because of this deficiency, SR males are able to fertilize only about half as many eggs as ST males. These results explain the observed equilibria of frequencies of SR in natural populations, and suggest that, at least in the case of D. pseudoobscura, male fertility may be partly limited by the number of sperm males can produce.
Analysis of irradiated Drosophila populations for meiotic drive
4510Novitski, EH, G. D., Nature, 190:989-990. 1961-01-08 00:00:00.
The existence of chromosomes or alleles that are represented in the gametes of a heterozygote with a frequency greater than the expected 50 percent is now well established for a variety of species. The immediate population result of introducing such a chromosome or allele must be a sharp increase in its frequency, alon with any other genes associated by linkage, independent of or, indeed, in spite of, their phenotypic effects. For this reason such phenomena have been referred to as cases of 'drive' and, more specifically, as 'meiotic drive' when the basis is found in some aberration of meiosis. Such instances would seem to provide an unparalleled opportunity for the study of population dynamics, for example, the efficacy of response of natural selection to unfavourable genes. It seemed worth while, therefore, to determine whether such chromosomes or alleles characterized by drive might be induced in the laboratory.
Meiotic drive in natural populations of Drosophila melanogaster .6: A preliminary report on presence of segregation-distortion in a Baja california population
4509Mange, EJ, American Naturalist, 95:87-96. 1961-01-07 00:00:00.
Meiotic drive is a term coined by Sandler and Novitski (1957) to describe; the situation whereby a heterozygote produces gametes containing an excess; of one allele, rather than the expected equality. As a consequence of such; aberrant segregations, gene frequencies within a population may be radically; altered; indeed, detrimental or lethal genes closely linked to the driven gene; may increase in frequency, thereby leading to a reduction in fitness or pos; sibly even to extinction of the population.; An instance of meiotic drive in Drosophila melanogaster, discovered by; Hiraizumi in a Madison, Wisconsin, population, has been reported by Sandler,; Hiraizumi and Sandler (1959). The phenomenon, termed segregation-distortion,; was found to depend upon a locus designated SD, which is located in the; centromeric heterochromatin of chromosome II. The phenomenon is ex; pressed in males only.; Since segregation-distortion was originally found in a natural population,; the question arose as to whether the phenomenon is of recent origin and; therefore localized in the vicinity of Madison, or well established and hence; widespread among natural populations of Drosophila melanogaster. There; fore, the screening of wild populations for SD (or for any other type of aber; rant segregation) was undertaken. In small samples from only thirteen popu; lations, SD has been detected in one Baja California population as well as; in three other rather widely separated Madison populations. This report will; be confined to establishing that the locus discovered in the southern Cape; region of Baja California (specifically, from Rancho La Burrera near the; west base of Sierra de La Laguna, and a Pleistocene lake relic, called; La Laguna, in the same range) is indeed SD.
Time of temperature sensitivity of meiotic drive in Drosophila melanogaster
4508Erickson, JH, G. D., American Naturalist, 95:247-250. 1961-01-06 00:00:00.
In a line of Drosophila melanogaster demonstrating meiotic drive, it was found that the high recovery rate of the X-chromosome could be nearly nullified by temperature treatment. A series of experiments were carried out to determine at what stage of the life-cycle this treatment is effective. The effect is observed to occur during a part of the process of spermatogenesis, either during the primary spermatocyte stage or extending through this and the meiotic divisions which follow.

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