Modelling homing suppression gene drive in haplodiploid organisms

Abstract

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 the characteristics of homing suppression gene drives in haplodiploids and find that a drive targeting a female fertility gene could still be successful. However, such drives are less powerful than in diploids. They are substantially more vulnerable to high resistance allele formation in the embryo due to maternally deposited Cas9 and gRNA and also to somatic cleavage activity. Examining models of continuous space where organisms move over a landscape, we find that haplodiploid suppression drives surprisingly perform nearly as well as in diploids, possibly due 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.

Adversarial interspecies relationships facilitate population suppression by gene drive in spatially explicit models

“…In this scenario, the migration rate is also important because it will determine the initial degree of population overlap between the two species, together with the competition factor. As expected, higher migration results in more suppression outcomes, while low migration results in more drive loss outcomes (Figure 5), consistent with previous results 15, 17, 20 .…”

“…For simulations where chasing occurred before suppression, the period of chasing was usually short, but when competing species size and competition factor are low, chasing could last for several hundred generations (Figure S2). Though chasing can make drives more vulnerable to complete failure by functional resistance allele formation 15, 17 , the existence of this phenomenon does not prevent potentially substantial benefits from being achieved, depending on the specific drive application. Specifically, reductions in female reproductive capacity could reduce the fertile female population compared to its initial state (Figure S2).…”

“…This is because gene drive individuals may struggle to find a potential mate in a limited distance after the population is sufficiently suppressed, removing the gene drive form the population while clusters of wild-type individuals still remain (at which point they could quickly repopulate the arena). This outcome is usually rare in one-species models for suppression drives targeting female fertility genes 15, 17 . However, drive loss is substantially more common in our model of competing species (Figure 2).…”

“…In this situation, wild-type individuals might benefit from the lack of competition in empty areas cleared by the drive, allowing them to quickly reproduce before the drive arrive again from an adjacent region. The drive and wild-type alleles could coexist until the end of simulation, with the drive "chasing" the wild-type alleles but never eliminating them all [15][16][17][18][19][20] . To avoid this situation and quickly eliminate a population, higher overall drive quality is required 15,17 .…”

Experimental demonstration of tethered gene drive systems for confined population modification or suppression

“…This could increase the efficiency of the homing drive, which generally suffers from embryo cutting. However, modeling indicates that a homing drive with high drive conversion efficiency or lacking significant fitness costs would still be able to tolerate high embryo cut rates, as long as functional resistance alleles did not form 20,56,57 .…”