Gene-drive-mediated extinction is thwarted by population structure and evolution of sib mating

Abstract

Background and objectives Genetic engineering combined with CRISPR technology has developed to the point that gene drives can, in theory, be engineered to cause extinction in countless species. Success of extinction programs now rests on the possibility of resistance evolution, which is largely unknown. Depending on the gene-drive technology, resistance may take many forms, from mutations in the nuclease target sequence (e.g. for CRISPR) to specific types of non-random population structures that limit the drive (that may block potentially any gene-drive technology). Methodology We develop mathematical models of various deviations from random mating to consider escapes from extinction-causing gene drives. A main emphasis here is sib mating in the face of recessive-lethal and Y-chromosome drives. Results Sib mating easily evolves in response to both kinds of gene drives and maintains mean fitness above 0, with equilibrium fitness depending on the level of inbreeding depression. Environmental determination of sib mating (as might stem from population density crashes) can also maintain mean fitness above 0. A version of Maynard Smith’s haystack model shows that pre-existing population structure can enable drive-free subpopulations to be maintained against gene drives. Conclusions and implications Translation of mean fitness into population size depends on ecological details, so understanding mean fitness evolution and dynamics is merely the first step in predicting extinction. Nonetheless, these results point to possible escapes from gene-drive-mediated extinctions that lie beyond the control of genome engineering. Lay summary Recent gene drive technologies promise to suppress and even eradicate pests and disease vectors. Simple models of gene-drive evolution in structured populations show that extinction-causing gene drives can be thwarted both through the evolution of sib mating as well as from purely demographic processes that cluster drive-free individuals.

Suppression gene drive in continuous space can result in unstable persistence of both drive and wild-type alleles

“…Outcomes consistent with chasing behavior have already been observed in other models of suppression gene drives in structured populations 22,24,26 . In these studies, it was generally suggested that the drive efficiency should be high enough to avoid drive loss due to drift but should not be so high that the drive eliminates patches of wild-type and itself before being able to spread to an adjacent region.…”

“…Evolution of an increased tendency for inbreeding has been suggested as a mechanism by which populations could avoid the suppressive effects of a gene drive 26 , and our studies in continuous space support this notion. We found that higher levels of inbreeding can indeed substantially reduce the effectiveness of the drive by increasing the likelihood of chasing.…”

“…The effect of inbreeding on chasing. Previous studies have found that inbreeding can pose a substantial obstacle to the spread of a gene drive 26,40 . To test whether these results extend to our spatial model and explore possible connections to the chasing phenomenon, we studied how varying the probability of matings between siblings affected drive outcomes in our spatial model.…”

“…For example, in a mosquito-specific simulation of a malaria-endemic nation represented by a network of linked panmictic populations, "metapopulation dynamics" were frequently observed, wherein a drive invasion resulted in local population elimination, which was then followed by recolonization by wild-type individuals 24 . Another study showed that an equilibrium can exist between empty space, regions with only wild-type alleles, and regions also containing drive alleles 26 .…”

Natural gene drives offer potential pathogen control strategies in plants

“…Fusarium graminearum is a homothallic fungus, meaning that it undergoes selfing and outcrossing. In nature, both modes of reproduction are known to occur (Goswami & Kistler, 2004;Trail, 2009), and while outcrossing promotes spread, selfing could potentially limit the drive's spread in populations (Bull et al, 2019). To test if drive could also be observed under random mating in F. graminearum, we crossed the drive and tester strains and monitored resulting genotypes in randomly mating populations (i.e.…”