Abstract
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.
Highlights
Invasive rodent populations occupy more than 80% of islands worldwide where they commonly pose significant threats to endemic biodiversity, as well as agricultural production and human health (Howald et al, 2007; Jones et al, 2016; Meerburg et al, 2009)
We identified 40 unique female fertility genes with Cas9 targets in the coding sequences (CDS) or 5′UTR that were fixed in the island population (Table S7)
In the Honolulu population, which was established from anthropogenic introductions to the island of Oahu, both measures of allelic diversity (SNP-He and Watterson's θ) were more similar to continental populations compared to other islands in the dataset (Figure 2a,b), suggesting a relatively large and genetically diverse population on Oahu and supporting its inclusion as a “continental” source population in our study design
Summary
Invasive rodent populations occupy more than 80% of islands worldwide where they commonly pose significant threats to endemic biodiversity, as well as agricultural production and human health (Howald et al, 2007; Jones et al, 2016; Meerburg et al, 2009). Management efforts to date have relied heavily on chemical rodenticides, which can often be prohibitively expensive or logistically infeasible for many island applications, and incur substantial costs in terms of environmental burden and off-target species mortality (Nakayama et al, 2019). These shortcomings, along with the advent of precision genome editing afforded by CRISPR-Cas technologies, have motivated interest in the development of synthetic gene drives for rodent population suppression (Campbell et al, 2015; Godwin et al, 2019; Gould, 2008; Piaggio et al, 2017; Rode et al, 2019). The self-replicating nature of homing endonuclease gene drive systems, wherein target sequences are cut and the gene drive elements copied to the homologous chromosome via homology directed repair (HDR or “homing”), is an attractive feature for eradication efforts on remote or difficult to access islands where repeated treatments can be impractical (Leitschuh et al, 2018)
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