Locally Fixed Alleles: A method to localize gene drive to island populations

Abstract

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.

Designing gene drives to limit spillover to non-target populations

“…Several approaches have been recently proposed for mitigating spillovers, involving complex gene drive architectures and deployment strategies [39,[62][63][64][65][66][67][68][69], as well as for countermeasures to halt an ongoing gene drive [10,[70][71][72]. A few of these gene drive architectures have been demonstrated in laboratory settings [10,38,53,60,73].…”

Invasive Species Control and Resolution of Wildlife Damage Conflicts: A Framework for Chemical and Genetically Based Management Methods

“…Genetic methods of pest control potentially offer a useful alternative to these established approaches. Although engineered gene drives harnessing either natural or synthetic drive mechanisms are still in the development phase, population modeling supports their potential effectiveness in reducing invasive mammal populations (Backus and Gross 2016;Prowse et al 2017Prowse et al , 2019Sudweeks et al 2019). As detailed above, harnessing natural or synthetic selfish genetic elements in the form of gene drives could provide options not burdened by many of the drawbacks of rodenticide-based approaches.…”

“…This work emphasizes that understanding factors that affect successful homing is a critical avenue for empirical research (Prowse et al 2017). To date, models of gene drive systems have focused primarily on combined population genetic-dynamic models of a two-deme or island-mainland system (Dhole et al 2018;Edgington and Alphey 2018;Sudweeks et al 2019). However, individual-level spatial processes due to social structure or movement behavior, and mating structure, can have important consequences for structuring genetic variation in space, suggesting that these are important future directions for models and experiments to explore.…”

“…Thus, population specificity might be accomplished through designing sgRNA that bind genomic regions harboring polymorphisms that form a functional PAM site in the target populations, but not in nontarget populations. Recent modeling efforts (Sudweeks et al 2019) demonstrate that such an approach can effectively achieve localized population suppression under a variety of scenarios. Interestingly, this work suggests that escape and interbreeding of gene-drive-bearing individuals out of the treatment area are likely to result in only transient suppression of nontarget populations, even when the "susceptible" (i.e., target) allele is present at high frequencies.…”

Double drives and private alleles for localised population genetic control

“…Alternatively, if there are pre-existing sequence differences between target and non-target populations, it may be possible to exploit these differences with a sequence-specific nuclease-based gene drive that would only spread in the target population, in which case the small release rates and overall efficiency of low threshold gene drive approaches may be retained [ 22 , 23 ]. Sudweeks et al [ 23 ] present useful modelling of this approach, considering the case where there is a locally fixed allele of an essential gene in the target population, while non-target populations carry a functional cleavage-resistant allele at some frequency. A single-locus gene drive that uses the homing reaction (i.e., sequence-specific cleavage followed by homologous repair [ 4 , 24 ]) to disrupt the locally fixed allele could be released into and eliminate the target population, but have little impact, or only a transient impact, on non-target populations.…”