Modelling homing suppression gene drive in haplodiploid organisms

Y. Liu and J. Champer,  Proceedings of the Royal Society B: Biological Sciences,  289:20220320. 2022.

Gene drives have shown great promise for suppression of pest populations. These engineered alleles can function by a variety of mechanisms, but the most common is the CRISPR homing drive, which converts wild-type alleles to drive alleles in the germline of heterozygotes. Some potential target species are haplodiploid, in which males develop from unfertilized eggs and thus have only one copy of each chromosome. This prevents drive conversion, a substantial disadvantage compared to diploids where drive conversion can take place in both sexes. Here, we study homing suppression gene drives in haplodiploids and find that a drive targeting a female fertility gene could still besuccessful. However, such drives are less powerful than in diploids and suffer more from functional resistance alleles. They are substantially more vulnerable to high resistance allele formation in the embryo owing to maternally deposited Cas9 and guide RNA and also to somatic cleavage activity. Examining spatial models where organisms move over a continuous land-scape, we find that haplodiploid suppression drives surprisingly perform early as well as in diploids, possibly owing to their ability to spread further before inducing strong suppression. Together, these results indicate that gene drive can potentially be used to effectively suppress haplodiploid populations.

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