Harnessing Wolbachia cytoplasmic incompatibility alleles for confined gene drive: A modeling study

Abstract

Wolbachia are maternally-inherited bacteria, which can spread rapidly in populations by manipulating reproduction. cifA and cifB are genes found in Wolbachia phage that are responsible for cytoplasmic incompatibility, the most common type of Wolbachia reproductive interference. In this phenomenon, no viable offspring are produced when a male with both cifA and cifB (or just cifB in some systems) mates with a female lacking cifA. Utilizing this feature, we propose new types of toxin-antidote gene drives that can be constructed with only these two genes in an insect genome, instead of the whole Wolbachia bacteria. By using both mathematical and simulation models, we found that a drive containing cifA and cifB together creates a confined drive with a moderate to high introduction threshold. When introduced separately, they act as a self-limiting drive. We observed that the performance of these drives is substantially influenced by various ecological parameters and drive characteristics. Extending our models to continuous space, we found that the drive individual release distribution has a critical impact on drive persistence. Our results suggest that these new types of drives based on Wolbachia transgenes are safe and flexible candidates for genetic modification of populations.

Transgenic expression ofcifgenes fromWolbachiastrainwAlbB recapitulates cytoplasmic incompatibility inAedes aegypti

“…Furthermore, the severe and growing public health burden of Ae. aegypti , its tractability in the laboratory, and the potential for building high-threshold gene drive systems using the cif genes 39 , makes studies on cif gene function in this species particularly timely and relevant. Although considerable research on the effects of cif gene expression using transgenic tools has been conducted in D. melanogaster 1,2,6–8,10,12 , the synthetic recapitulation of CI using the cif genes in Aedes mosquitoes has not yet been reported.…”

“…aegypti populations. Mathematical modelling of drive systems based on the cif genes in various design configurations suggests that they will possess high invasion-threshold frequencies, and thus are likely to be inherently more confinable to target populations than analogous homing drive systems; by splitting the induction and rescue components the drive could be further confined temporally as well as spatially 39 . Consequently, these drive designs are expected to be more easily controlled and regulated from a biosafety and geopolitical perspective.…”

Cleave and Rescue gamete killers create conditions for gene drive in plants

“…The death of those lacking the TA cassette can result in a relative increase in frequency of those carrying it. Modeling shows that TA elements in sexually reproducing eukaryotes can (depending on the fitness costs associated with carriage of the element and introduction frequency) spread to high frequency even if they do not confer any advantage to their hosts [8][9][10][11][12][13][14][15][16][17][18] .…”

Assessment of distant-site rescue elements for CRISPR toxin-antidote gene drives

“…Several options exist for confined gene drives ( Hay et al, 2021 ; Wang et al, 2022 ), including Medea ( Chen et al, 2007 ), haploinsufficient underdominance ( Reeves et al, 2014 ), chromosomal rearrangements ( Foster et al, 1972 ; Buchman et al, 2018 ), incompatibility underdominance ( Maselko et al, 2020 ), and Wolbachia cytoplasmic incompatibility drive ( Li and Champer, 2022 ). Some of the latest confined drive designs are based on CRISPR nucleases.…”