Population genomics of invasive rodents on islands: Genetic consequences of colonization and prospects for localized synthetic gene drive

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.

Ultra-conserved sequences in the genomes of highly diverse Anopheles mosquitoes, with implications for malaria vector control

“…There may be some circumstances, for example, for phased testing of a gene drive’s efficacy and safety, where it is desirable to target a sequence that is unique to a particular population. For this, it would be interesting to explore conserved sites that show polymorphisms within species, a prospect that is being explored for mosquito and rodent control ( Oh et al 2021 ; Willis and Burt 2021 ).…”

Double drives and private alleles for localised population genetic control

“…Note that the single drives modelled by Sudweeks et al [23] require the opposite type of differentiation: sequences that are fixed in the target population, even if not private (i.e., even if found at appreciable frequencies in the non-target population [61]). In this latter scenario the challenge is not so much to have an impact on the target population as to not have an impact on the non-target population.…”

The Promise of Genetics and Genomics for Improving Invasive Mammal Management on Islands

“…A gene drive is a naturally occurring phenomenon of biased inheritance that can be bioengineered into a target species to ensure that specific allele(s) are transmitted to the next generation at a much higher rate than the 50% expected under Mendelian inheritance (Burt and Trivers, 2006;Burt and Crisanti, 2018). The harnessing of gene drive technology is being explored as a means to potentially transform invasive species management by editing genomes to control populations in various ways, effectively eliminating the need for pesticides or other tools, while also increasing the efficiency and lessening the risks of IMS control or eradication on islands (Oh et al, 2021). The harnessing of CRISPR-Cas9 mediated genetic engineering has greatly enhanced the potential of gene drives by facilitating the spread of a targeted gene up to 100% in a population (National Academies of Sciences, Engineering, and Medicine (NASEM), 2016).…”

“…Deploying a novel gene drive in mainland systems has greater risk of undesirable consequences as habitat is generally less fragmented and more conducive to gene flow. Additionally, island species contain relatively low levels of genetic diversity compared to mainland conspecifics due to historical founder effects, making insular populations more likely to carry locally fixed alleles that are excellent targets for gene drive technology (Sudweeks et al, 2019;Oh et al, 2021). Importantly, assessing the risks of synthetic biology remains a focus of discussion in global policy arenas such as the United Nations, where gene drives are currently regulated under the Cartagena Protocol on Biosafety to the Convention on Biological Diversity (Keiper and Atanassova, 2020).…”