Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach, but the potential for drive-bearing individuals to escape from the target release area and impact populations elsewhere is a major concern. Here we propose the "Locally Fixed Alleles" approach as a novel means for localizing elimination by a drive to an island population that exhibits significant genetic isolation from neighboring populations. Our approach is based on the assumption that in small island populations of rodents, genetic drift will lead to multiple genomic alleles becoming fixed. In contrast, multiple alleles are likely to be maintained in larger populations on mainlands. Utilizing the high degree of genetic specificity achievable using homing drives, for example based on the CRISPR/Cas9 system, our approach aims at employing one or more locally fixed alleles as the target for a gene drive on a particular island. Using mathematical modeling, we explore the feasibility of this approach and the degree of localization that can be achieved. We show that across a wide range of parameter values, escape of the drive to a neighboring population in which the target allele is not fixed will at most lead to modest transient suppression of the non-target population. While the main focus of this paper is on elimination of a rodent pest from an island, we also discuss the utility of the locally fixed allele approach for the goals of population suppression or population replacement. Our analysis also provides a threshold condition for the ability of a gene drive to invade a partially resistant population. 1R01AI139085-01 (FG and ALL) and the NC State Drexel Endowment (ALL). Contributions from other members of the Genetic Biocontrol of Invasive Rodents (GBIRd) consortium (http://www.geneticbiocontrol.org/) are acknowledged and greatly appreciated. We thank the referees for their constructive comments that helped improve this paper. Author ContributionsJS, BH, FG and ALL designed the model. JS, BH and ALL carried out model simulations and analysis. JS, BH, FG and ALL wrote the first draft of the paper. All authors discussed model results and contributed to editing and revision of the manuscript.

Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach, but the potential for drive-bearing individuals to escape from the target release area and impact populations elsewhere is a major concern. Here we propose the “Locally Fixed Alleles” approach as a novel means for localizing elimination by a drive to an island population that exhibits significant genetic isolation from neighboring populations. Our approach is based on the assumption that in small island populations of rodents, genetic drift will lead to alleles at multiple genomic loci becoming fixed. In contrast, multiple alleles are likely to be maintained in larger populations on mainlands. Utilizing the high degree of genetic specificity achievable using homing drives, for example based on the CRISPR/Cas9 system, our approach aims at employing one or more locally fixed alleles as the target for a gene drive on a particular island. Using mathematical modeling, we explore the feasibility of this approach and the degree of localization that can be achieved. We show that across a wide range of parameter values, escape of the drive to a neighboring population in which the target allele is not fixed will at most lead to modest transient suppression of the non-target population. While the main focus of this paper is on elimination of a rodent pest from an island, we also discuss the utility of the locally fixed allele approach for the goals of population suppression or population replacement. Our analysis also provides a threshold condition for the ability of a gene drive to invade a partially resistant population.

Invasive rodents impact biodiversity, human health and food security worldwide. The biodiversity impacts are particularly significant on islands, which are the primary sites of vertebrate extinctions and where we are reaching the limits of current control technologies. Gene drives may represent an effective approach to this challenge, but knowledge gaps remain in a number of areas. This paper is focused on what is currently known about natural and developing synthetic gene drive systems in mice, some key areas where key knowledge gaps exist, findings in a variety of disciplines relevant to those gaps and a brief consideration of how engagement at the regulatory, stakeholder and community levels can accompany and contribute to this effort. Our primary species focus is the house mouse, Mus musculus , as a genetic model system that is also an important invasive pest. Our primary application focus is the development of gene drive systems intended to reduce reproduction and potentially eliminate invasive rodents from islands. Gene drive technologies in rodents have the potential to produce significant benefits for biodiversity conservation, human health and food security. A broad-based, multidisciplinary approach is necessary to assess this potential in a transparent, effective and responsible manner.

Introduced rodent populations pose significant threats worldwide, with particularly severe impacts on islands. Advancements in genome editing have motivated interest in synthetic gene drives that could potentially provide efficient and localized suppression of invasive rodent populations. Application of such technologies will require rigorous population genomic surveys to evaluate population connectivity, taxonomic identification, and to inform design of gene drive localization mechanisms. One proposed approach leverages the predicted shifts in genetic variation that accompany island colonization, wherein founder effects, genetic drift, and island‐specific selection are expected to result in locally fixed alleles (LFA) that are variable in neighboring nontarget populations. Engineering of guide RNAs that target LFA may thus yield gene drives that spread within invasive island populations, but would have limited impacts on nontarget populations in the event of an escape. Here we used pooled whole‐genome sequencing of invasive mouse (Mus musculus) populations on four islands along with paired putative source populations to test genetic predictions of island colonization and characterize locally fixed Cas9 genomic targets. Patterns of variation across the genome reflected marked reductions in allelic diversity in island populations and moderate to high degrees of differentiation from nearby source populations despite relatively recent colonization. Locally fixed Cas9 sites in female fertility genes were observed in all island populations, including a small number with multiplexing potential. In practice, rigorous sampling of presumptive LFA will be essential to fully assess risk of resistance alleles. These results should serve to guide development of improved, spatially limited gene drive design in future applications.

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.

High population density is often associated with increased levels of stress-related hormones, such as corticosterone (CORT). Prairie voles (Microtus ochrogaster) are a socially monogamous species known for their large population density fluctuations in the wild. Although CORT influences the social behavior of prairie voles in the lab, the effect of population density on CORT has not previously been quantified in this species in the field. We validated a non-invasive hormone assay for measuring CORT metabolites in prairie vole feces. We then used semi-natural enclosures to experimentally manipulate population density, and measured density effects on male space use and fecal CORT levels. Our enclosures generated patterns of space use and social interaction that were consistent with previous prairie vole field studies. Contrary to the positive relationship between CORT and density typical of other taxa, we found that lower population densities (80 animals/ha) produced higher fecal CORT than high densities (240/ha). Combined with prior work in the lab and field, the data suggest that high prairie vole population densities indicate favorable environments, perhaps through reduced predation risk. Lastly, we found that field animals had lower fecal CORT levels than laboratory-living animals. The data emphasize the usefulness of prairie voles as models for integrating ecological, evolutionary and mechanistic questions in social behavior.

No abstract

BackgroundChina is characterized by complex topographic structure and dramatic palaeoclimatic changes, making species biogeography studies particularly interesting. Previous researchers have also demonstrated multiple species experienced complex population histories, meanwhile multiple shelters existed in Chinese mainland. Despite this, species phylogeography is still largely unexplored. In the present study, we used a combination of microsatellites and mitochondrial DNA (mtDNA) to investigate the phylogeography of the east Asian fish-eating bat (Myotis pilosus).ResultsPhylogenetic analyses showed that M. pilosus comprised three main lineages: A, B and C, which corresponded to distinct geographic populations of the Yangtze Plain (YTP), Sichuan Basin (SCB) and North and South of China (NSC), respectively. The most recent common ancestor of M. pilosus was dated as 0.25 million years before present (BP). Population expansion events were inferred for populations of Clade C, North China Plain region, Clade B and YunGui Plateau region at 38,700, 15,900, 4,520 and 4,520 years BP, respectively. Conflicting results were obtained from mtDNA and microsatellite analyses; strong population genetic structure was obtained from mtDNA data but not microsatellite data. The microsatellite data indicated that genetic subdivision fits an isolation-by-distance (IBD) model, but the mtDNA data failed to support this model.ConclusionsOur results suggested that Pleistocene climatic oscillations might have had a profound influence on the demographic history of M. pilosus. Spatial genetic structures of maternal lineages that are different from those observed in other sympatric bats species may be as a result of interactions among special population history and local environmental factors. There are at least three possible refugia for M. pilosus during glacial episodes. Apparently contradictory genetic structure patterns of mtDNA and microsatellite could be explained by male-mediated gene flow among populations. This study also provides insights on the necessity of conservation of M. pilosus populations to conserve this genetic biodiversity, especially in the areas of YTP, SCB and NSC regions.