Propagation of seminal toxins through binary expression gene drives could suppress populations

Image from McCullough et al (2022) doi: 10.1073/pnas.2119899119

Gene drives can be highly effective in controlling a target population by disrupting a female fertility gene. To spread across a population, these drives require that disrupted alleles be largely recessive so as not to impose too high of a fitness penalty. We argue that this restriction may be relaxed by using a double gene drive design to spread a split binary expression system. One drive carries a dominant lethal/toxic effector alone and the other a transactivator factor, without which the effector will not act. Only after the drives reach sufficiently high frequencies would individuals have the chance to inherit both system components and the effector be expressed. We explore through mathematical modeling the potential of this design to spread dominant lethal/toxic alleles and suppress populations. We show that this system could be implemented to spread engineered seminal proteins designed to kill females, making it highly effective against polyandrous populations.

Figure 1. Binary expression drive constructs. Left: the transactivator construct (a). Right: the effector construct (b). The promoter of the transactivator gene is only active in the target tissue/organ, for instance, the ovaries or the male accessory glands. The transactivator protein will activate the expression of the effector gene, which encodes a dominant or semidominant toxin, in the target tissue/organ. In both constructs, the expression of Cas9 and the gRNA is under the regulation of a germline promoter that allows drive conversion during meiosis. Ideally, target loci are highly conserved genes that cannot tolerate mutations so resistance alleles are selected out of the population while each drive allele alone, carrying a re-coded target gene, will not impose an intended fitness cost.
Image from Hurtado et al (2022) doi: 10.1038/s41598-022-10327-4

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