RESUMO
House mice (Mus musculus) have spread globally as a result of their commensal relationship with humans. In the form of laboratory strains, both inbred and outbred, they are also among the most widely used model organisms in biomedical research. Although the general outlines of house mouse dispersal and population structure are well known, details have been obscured by either limited sample size or small numbers of markers. Here we examine ancestry, population structure, and inbreeding using SNP microarray genotypes in a cohort of 814 wild mice spanning five continents and all major subspecies of Mus, with a focus on M. m. domesticus. We find that the major axis of genetic variation in M. m. domesticus is a south-to-north gradient within Europe and the Mediterranean. The dominant ancestry component in North America, Australia, New Zealand, and various small offshore islands are of northern European origin. Next we show that inbreeding is surprisingly pervasive and highly variable, even between nearby populations. By inspecting the length distribution of homozygous segments in individual genomes, we find that inbreeding in commensal populations is mostly due to consanguinity. Our results offer new insight into the natural history of an important model organism for medicine and evolutionary biology.
Assuntos
Genoma , Endogamia , Animais , Evolução Biológica , Europa (Continente) , Humanos , Camundongos , Nova ZelândiaRESUMO
The Judas technique is often used in control or eradication of particular vertebrate pests. The technique exploits the tendency of individuals to form social groups. A radio collar is affixed to an individual and its subsequent monitoring facilitates the detection of other conspecifics. Efficacy of this technique would be improved if managers could estimate the probability that a Judas individual would detect conspecifics. To calculate this probability, we estimated association rates of Judas individuals with other Judas individuals, given the length of time the Judas has been deployed. We developed a simple model of space-use for individual Judas animals and constrained detection probabilities to those specific areas. We then combined estimates for individual Judas animals to infer the probability that a wild individual could be detected in an area of interest via Judas surveillance. We illustrated the method by using data from a feral goat eradication program on Isla Santiago, Galápagos, and a feral pig eradication program on Santa Cruz Island, California. Association probabilities declined as the proximity between individual areas of use of a Judas pair decreased. Unconditional probabilities of detection within individual areas of use averaged 0.09 per month for feral pigs and 0.11 per month for feral goats. Probabilities that eradication had been achieved, given no detections of wild conspecifics, and an uninformative prior probability of eradication were 0.79 (90% CI 0.22-0.99) for feral goats and 0.87 (90% CI 0.44-1.0) for feral pigs. We envisage several additions to the analyses used that could improve estimates of Judas detection probability. Analyses such as these can help managers increase the efficacy of eradication efforts, leading to more effective effects to restore native biodiversity.
La técnica de Judas se usa con frecuencia en el control de ciertas plagas de vertebrados. La técnica se aprovecha de la tendencia a formar grupos sociales que tienen los individuos. Un radio-collar es colocado en uno de los individuos y el monitoreo subsecuente facilita la detección de otros miembros de la misma especie. La eficacia de esta técnica mejoraría si los gestores pudieran estimar la probabilidad que tiene un Judas de detectar a miembros de su especie. Para calcular esta probabilidad, estimamos las tasas de asociación de los Judas con otros Judas, dado el tiempo que el Judas ha sido enviado. Desarrollamos un modelo simple del uso del espacio para animales Judas individuales y limitamos las probabilidades de detección a esas áreas específicas. Después combinamos los estimados de un animal Judas individual para inferir la probabilidad de que un individuo silvestre pudiera ser detectado en un área de interés mediante la vigilancia Judas. Ilustramos el método con los datos de un programa de erradicación de cabras ferales en Isla Santiago, las Galápagos, y uno de cerdos ferales en la Isla de Santa Cruz, California. Las probabilidades de asociación declinaron conforme disminuyó la proximidad entre las áreas individuales de uso de un par de Judas. Las probabilidades incondicionales de detección dentro de las áreas individuales de uso promediaron 0.09 por mes para los cerdos ferales y 0.11 por mes para las cabras ferales. Las probabilidades de que se había logrado la erradicación, dada la ausencia de detecciones de miembros de la misma especie y una mal informada probabilidad previa de erradicación, fueron de 0.79 (90% CI 0.22 - 0.99) para las cabras ferales y 0.87 (90% CI 0.44 - 1.0) para los cerdos ferales. Contemplamos varias adiciones al análisis que usamos que podrían mejorar los estimados de la probabilidad de detección de Judas. Análisis como este pueden ayudar a los gestores a incrementar la efectividad de los esfuerzos de erradicación, lo que resulta en efectos más efectivos para restaurar la biodiversidad nativa.
Assuntos
Animais Selvagens , Conservação dos Recursos Naturais , Animais , Biodiversidade , Conservação dos Recursos Naturais/métodos , Probabilidade , VertebradosRESUMO
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.
RESUMO
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.
Assuntos
Alelos , Biodiversidade , Animais , IlhasRESUMO
Anticoagulant rodenticides are used to manage rodents in domestic, municipal, agricultural, and conservation settings. In mammals and birds, anticoagulant poisoning causes extensive hemorrhagic disruption, with the primary cause of death being severe internal bleeding occurring over days. The combined severity and duration of these effects represent poor welfare outcomes for poisoned animals. Noting a lack of formal estimates of numbers of rodents and nontarget animals killed by anticoagulant poisoning, the ready availability and worldwide use of anticoagulants suggest that very large numbers of animals are affected globally. Scrutiny of this rodent control method from scientific, public, and regulatory perspectives is being driven largely by mounting evidence of environmental transfer of residual anticoagulants resulting in harmful exposure in wild or domestic animals, but there is also nascent concern for the welfare of targeted rodents. Rodent control incurs a cumulative ledger of animal welfare costs over time as target populations reduced by poisoning eventually recover to an extent requiring another reduction. This 'rolling toll' presents a critical contrast to the animal welfare accountancy ledger for eradication scenarios, where rodent populations can be completely removed by methods including anticoagulant use and then kept from coming back (e.g., on islands). Successful eradications remove any future need to control rodents and to incur the associated animal welfare costs.
RESUMO
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 in multiple 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.
Assuntos
Proteínas Nucleares/genética , Proteínas de Ligação a RNA/genética , Sequências Repetitivas de Ácido Nucleico , Adaptação Fisiológica/genética , Alelos , Animais , Evolução Biológica , Variações do Número de Cópias de DNA/genética , Evolução Molecular , Feminino , Variação Genética , Genética Populacional , Masculino , Camundongos , Modelos Genéticos , Mutação , Seleção GenéticaRESUMO
Invasive alien mammals are the major driver of biodiversity loss and ecosystem degradation on islands. Over the past three decades, invasive mammal eradication from islands has become one of society's most powerful tools for preventing extinction of insular endemics and restoring insular ecosystems. As practitioners tackle larger islands for restoration, three factors will heavily influence success and outcomes: the degree of local support, the ability to mitigate for non-target impacts, and the ability to eradicate non-native species more cost-effectively. Investments in removing invasive species, however, must be weighed against the risk of reintroduction. One way to reduce reintroduction risks is to eradicate the target invasive species from an entire archipelago, and thus eliminate readily available sources. We illustrate the costs and benefits of this approach with the efforts to remove invasive goats from the Galápagos Islands. Project Isabela, the world's largest island restoration effort to date, removed >140,000 goats from >500,000 ha for a cost of US$10.5 million. Leveraging the capacity built during Project Isabela, and given that goat reintroductions have been common over the past decade, we implemented an archipelago-wide goat eradication strategy. Feral goats remain on three islands in the archipelago, and removal efforts are underway. Efforts on the Galápagos Islands demonstrate that for some species, island size is no longer the limiting factor with respect to eradication. Rather, bureaucratic processes, financing, political will, and stakeholder approval appear to be the new challenges. Eradication efforts have delivered a suite of biodiversity benefits that are in the process of revealing themselves. The costs of rectifying intentional reintroductions are high in terms of financial and human resources. Reducing the archipelago-wide goat density to low levels is a technical approach to reducing reintroduction risk in the short-term, and is being complemented with a longer-term social approach focused on education and governance.