Spatial gene drives and pushed genetic waves

Tanaka, HS, Howard A.; Nelson, David R.,  Proceedings of the National Academy of Sciences of the United States of America,  114:8452. 2017.

Gene constructs introduced into natural environments have been proposed to solve various ecological problems. The CRISPR-Cas9 technology greatly facilitates construction of gene drives that allow desired traits to rapidly replace wild types, even if these convey a selective growth rate disadvantage s > 0. However, accidental release of a gene drive could damage ecosystems irreversibly. We have modeled the spatial spread of gene drives and find a preferred range of selective disadvantages, 0.5 < s < 0.697. In this regime, gene drives spread but only when a nucleus exceeds a critical size and intensity. By making gene drives uniquely susceptible to a compound, their advance can be stopped in two dimensions by finite-width barriers, even when interrupted by gaps.Gene drives have the potential to rapidly replace a harmful wild-type allele with a gene drive allele engineered to have desired functionalities. However, an accidental or premature release of a gene drive construct to the natural environment could damage an ecosystem irreversibly. Thus, it is important to understand the spatiotemporal consequences of the super-Mendelian population genetics before potential applications. Here, we use a reaction–diffusion model for sexually reproducing diploid organisms to study how a locally introduced gene drive allele spreads to replace the wild-type allele, although it possesses a selective disadvantage s > 0. Using methods developed by Barton and collaborators, we show that socially responsible gene drives require 0.5 < s < 0.697, a rather narrow range. In this “pushed wave” regime, the spatial spreading of gene drives will be initiated only when the initial frequency distribution is above a threshold profile called “critical propagule,” which acts as a safeguard against accidental release. We also study how the spatial spread of the pushed wave can be stopped by making gene drives uniquely vulnerable (“sensitizing drive”) in a way that is harmless for a wild-type allele. Finally, we show that appropriately sensitized drives in two dimensions can be stopped, even by imperfect barriers perforated by a series of gaps.