Invasion and migration of self-limiting gene drives: a comparative analysis

Abstract

Recent advances in research on gene drives have produced genetic constructs that could theoretically spread a desired gene (payload) into all of the populations of a targeted species, with a single release in one place. This attribute has advantages, but also comes with risks and ethical concerns. There has been a call for research on gene drive systems that are spatially and/or temporally self-limiting. Here we use a population genetics model to compare the expected characteristics of three self-limiting gene drive systems: one-locus underdominance, two-locus underdominance, and daisy-chain drive. We find large differences between the self-limiting gene drives in the minimum number of engineered individuals that need to be released for successfully driving a payload into an isolated population. The daisy-chain system is the most efficient, requiring the smallest release, followed by the two-locus underdominance system. The one-locus underdominance system requires the largest releases for successful drive to occur. However, when the target population exchanges migrants with a non-target population, the gene drives requiring smaller releases suffer from higher risks of unintended spread. For payloads that incur relatively low fitness costs (up to 30%), a simple daisy-chain drive is practically incapable of remaining localized, even with migration rates as low as 1% per generation. The two-locus underdominance system can achieve localized spread under a broader range of migration rates and of payload fitness costs, while the one-locus underdominance system largely remains localized. We also find differences in the extent of population alteration and in the permanence of the alteration achieved by the three gene drives. The two-locus underdominance system does not always spread the payload to fixation, even after successful drive, while the daisy-chain system can, in some cases, achieve a temporally-limited spread of the payload. These differences could affect the suitability of each gene drive for specific applications. We ask all readers to recognize that this article has not yet been peer reviewed, and thus, the results shown herein have not yet been validated by researchers other than the authors. We suggest that any reference to or quotation of this article should be made with this recognition.