Controlling invasive rodents via synthetic gene drive and the role of polyandry

Abstract

House mice are a major ecosystem pest, particularly threatening island ecosystems as a non-native invasive species. Rapid advances in synthetic biology offer new avenues to control pest species for biodiversity conservation. Recently, a synthetic sperm-killing gene drive construct called t-Sry has been proposed as a means to eradicate target mouse populations owing to a lack of females. A factor that has received little attention in the discussion surrounding such drive applications is polyandry. Previous research has demonstrated that sperm-killing drivers are extremely damaging to a male’s sperm competitive ability. Here, we examine the importance of this effect on the t-Sry system using a theoretical model. We find that polyandry substantially hampers the spread of t-Sry such that release efforts have to be increased three- to sixfold for successful eradication. We discuss the implications of our finding for potential pest control programmes, the risk of drive spread beyond the target population, and the emergence of drive resistance. Our work highlights that a solid understanding of the forces that determine drive dynamics in a natural setting is key for successful drive application, and that exploring the natural diversity of gene drives may inform effective gene drive design.

Gene drive: progress and prospects

“…An advantage of co-opting an ancient drive system, in which suppressors have not been found, is that rapid evolution of resistance may be less of a problem. Manser et al [17] further explore this t haplotype-based synthetic driver, which is in development. The t haplotype is an autosomal sperm-killing driver that manipulates sperm, so that nearly all offspring from a heterozygous male inherit the t haplotype.…”

“…The idea is to introduce t-Sry to island mouse pest populations, thereby turning the entire population male and eliminating it altogether [18,19]. Manser et al [17] explore the population dynamics of the royalsocietypublishing.org/journal/rspb Proc. R. Soc.…”

“…The synthetic Medea driver developed for the crop pest Drosophila suzukii took inspiration from the natural drive system of the same name [30], known from Tribolium flour beetles [31]. The development of synthetic X chromosome shredders in mosquitoes [6] is preceded by the discovery in mosquitoes of a natural X chromosome shredder [32], and the synthetic sex ratio distorter being developed in house mice [17][18][19] is directly based on the modification of the t haplotype [33]. Courret et al [26] review the origins and mechanisms of the 19 known drivers in Drosophila, showing that nearly all of the well-characterized systems evolve from gene duplications and involve heterochromatin regulation, small RNA and/or nuclear transport pathways.…”

Rodent gene drives for conservation: opportunities and data needs

“…the t-haplotype in mice for an estimated 2.9 Myr [55]) and therefore probably be less prone to resistance development than the synthetic mechanisms developed to date. Second, modelling suggests that at least the t-Sry system would probably require multiple introductions in order to effectively suppress an invasive mouse population [47,56]. While this could reduce effectiveness and increase cost, concerns have been expressed about the uncontrolled spread of drive carriers [57,58].…”

“…We described the impressive degree of behavioural adaptation rodents show in island ecosystems at the beginning of this section. Such behavioural adaptations could represent mechanisms of resistance to gene drive spread as well in the form of inbreeding, mate choice and patterns of multiple mating (see [68] for polyandry and [56] for polygyny).…”