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 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.

Abundance of conserved CRISPR-Cas9 target sites within the highly polymorphic genomes of Anopheles and Aedes mosquitoes

“…2). A scenario where this might be useful is the targeting of small, defined populations, where spillover to neighboring populations is unwanted and can be avoided by the intended use of alleles that are fixed in the target population but absent in the neighbor population 34,35 . While this can also be applied with population modification strategies, these also can be specifically designed to have a negligible fitness cost relative to wild-type 12 .…”

Gene drive and resilience through renewal with next generationCleave and Rescueselfish genetic elements

“…Transgenes, or alleles of endogenous loci, can be linked with a genetic element conferring drive, and this can promote their spread. A number of approaches to spreading traits through populations (population replacement/alteration/modification) in ways that are self-sustaining, by linking them with genetic elements that mediate drive, have been proposed (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) . Several of these, Medea (9,23) , UD mel (15) , engineered translocations (24) , and ClvR ( Cleave and Rescue ) selfish genetic elements (25) , have been implemented and shown to spread to transgene fixation in otherwise wildtype Drosophila .…”

Gene drive and resilience through renewal with next generationCleave and Rescueselfish genetic elements

“…Transgenes, or alleles of endogenous loci, can be linked with a genetic element conferring drive, and this can promote their spread. A number of approaches to spreading traits through populations (population replacement/alteration/modification) in ways that are self-sustaining, by linking them with genetic elements that mediate drive, have been proposed (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Several of these, Medea (9, 23), UD mel (15), engineered translocations (24), and ClvR (Cleave and Rescue) selfish genetic elements (25), have been implemented and shown to spread to transgene fixation in otherwise wild-type (WT) Drosophila.…”