TY - JOUR T1 - Lethal Gene Drive Selects Escape through Inbreeding JF - bioRxiv DO - 10.1101/046847 SP - 046847 AU - J J. Bull Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/04/02/046847.abstract N2 - The use of ‘selfish’ gene drive systems to suppress or even extinguish populations has been proposed on theoretical grounds for almost half a century. Creating these genes has recently become possible with CRISPR technology. One seemingly feasible approach, originally proposed by Burt, is to create a homing endonuclease gene (HEG) that inserts into an essential gene, enabling heterozygote viability but causing homozygote lethality. With 100% segregation distortion in gametes, such genes can cause profound population suppression if resistance does not evolve. Here, population genetic models are used to consider the evolution of inbreeding (selfing) as a possible response to a recessively lethal HEG with complete segregation distortion. Numerical results indicate a rich set of outcomes, but selfing often evolves in response to the HEG. Whether selfing does indeed evolve and its effect in restoring population fitness depends heavily on the magnitude of inbreeding depression. Overall, these results point toward an underappreciated evolutionary response to block the harmful effects of a selfish gene. They raise the possibility that extreme population suppression may be more difficult to achieve than currently imagined. ER -