Y-linked editors for invasive rodent control

Abstract Invasive rodents are major contributors to biodiversity loss, particularly on islands where native species have evolved in their absence, rendering them vulnerable to predation. Genetic biocontrol offers a promising suite of species-specific technologies that may contribute to rodent suppression and elimination. Here, we evaluate the potential of Y-linked genome editors (YLEs), which contain a nuclease that disrupts a female-essential fertility or viability gene, to suppress or eliminate a mouse population on a small, isolated island. We benchmark YLEs against other self-limiting genetic biocontrol tools, such as sterile male releases, and self-sustaining tools, such as population suppression gene drives and Y-linked X chromosome-shredders. We use the MouseGD simulation framework to model the inheritance patterns of these systems in the context of rodent life history, calculating elimination probabilities, times to elimination and other outcomes for a range of construct designs, fitness costs and release schemes. We find that YLEs are more efficient than other self-limiting tools, and are capable of achieving rodent elimination within a short timeframe for modest release sizes. For a mouse population size of 10,000, elimination is predicted within five years for releases of 350 males per month, and within ten years for releases of 150 males per month. This scale of production is well within existing capabilities, potentially enabling suppression to encompass a larger spatial scale. We found that elimination could be achieved for YLEs targeting both haploinsufficient and haplosufficient target genes; but for a more restrictive parameter space for the haplosufficient case. Gene drives were predicted to achieve suppression and elimination for smaller release sizes; but also to spread to non-target populations. In contrast, YLEs do not bias inheritance and hence display minimal spillover. Altogether, these characteristics present YLEs as a promising, ecologically-manageable biocontrol tool for elimination of invasive rodents and conservation of native species. Competing Interest Statement OSA is a founder of Agragene, Inc. and Synvect, Inc. with equity interest. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. PV and JMM declare no competing interests.