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

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 suppre...

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Bibliographic Details
Published inbioRxiv
Main Authors Sudweeks, Jaye, Hollingsworth, Brandon, Blondel, Dimitri V, Campbell, Karl J, Dhole, Sumit, Eisemann, John D, Edwards, Owain, Godwin, John, Howald, Gregg R, Oh, Kevin, Piaggio, Antoinette J, Prowse, Thomas A A, Ross, Joshua V, J Royden Saah, Shiels, Aaron B, Thomas, Paul, Threadgill, David W, Vella, Michael R, Gould, Fred, Lloyd, Alun
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 07.09.2019
Subjects
Alleles
Biodiversity
CRISPR
Ecosystem assessment
Genetic drift
Genetic isolation
Introduced species
Invasive species
Localization
Mathematical models
Population genetics
Rodentia
Toxicants
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Summary: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 suppress 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 a suppression 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 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 across a wide range of parameter values. Footnotes * Supplementary Information: Addition of a sensitivity analysis; addition of a stochastic model and discussion of initial results from that model
DOI:10.1101/509364