A CRISPR endonuclease gene drive reveals two distinct mechanisms of inheritance bias

RNA guided CRISPR gene drives have shown the capability of biasing transgene inheritance in multiple species. Among these, homing endonuclease drives are the most developed. In this study, we report the functioning of sds3, bgcn, and nup50 expressed Cas9 in an Aedes aegypti homing split drive system targeting the white gene. We report their inheritance biasing capability, propensity for maternal deposition, and zygotic/somatic expression. Additionally, by making use of the tight linkage of white to the sex-determining locus, we were able to elucidate mechanisms of inheritance bias. We find inheritance bias through homing in double heterozygous males, but find that a previous report of the same drive occurred through meiotic drive. We propose that other previously reported ‘homing’ design gene drives may in fact bias their inheritance through other mechanisms with important implications for gene drive design.

More related to this:

A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deployment

A century of bias in genetics and evolution

Gene drive organisms not ready for environmental release

Transposable element insertion location bias and the dynamics of gene drive in mosquito populations

Persistence of an extreme sex-ratio bias in a natural population