Semele: A Killer-Male, Rescue-Female System for Suppression and Replacement of Insect Disease Vector Populations

Abstract

Two strategies to control mosquito-borne diseases, such as malaria and dengue fever, are reducing mosquito population sizes or replacing populations with disease-refractory varieties. We propose a genetic system, Semele, which may be used for both. Semele consists of two components: a toxin expressed in transgenic males that either kills or renders infertile wild-type female recipients and an antidote expressed in females that protects them from the effects of the toxin. An all-male release results in population suppression because wild-type females that mate with transgenic males produce no offspring. A release that includes transgenic females results in gene drive since females carrying the allele are favored at high population frequencies. We use simple population genetic models to explore the utility of the Semele system. We find that Semele can spread under a wide range of conditions, all of which require a high introduction frequency. This feature is desirable since transgenic insects released accidentally are unlikely to persist, transgenic insects released intentionally can be spatially confined, and the element can be removed from a population through sustained release of wild-type insects. We examine potential barriers to Semele gene drive and suggest molecular tools that could be used to build the Semele system.

Genetic control ofAedesmosquitoes

“…[89][90][91] This has a high invasion threshold making it relatively unlikely to invade non-target populations well isolated from any target populations. Medea-like systems have a much lower invasion threshold and so are much more likely to spread aggressively into distant populations, 86,87,92 though modifications can in principle be made to reduce this. 92 Transposons, long proposed as the basis for gene drive systems though not yet demonstrated, are also potentially highly invasive.…”

“…Medea-like systems have a much lower invasion threshold and so are much more likely to spread aggressively into distant populations, 86,87,92 though modifications can in principle be made to reduce this. 92 Transposons, long proposed as the basis for gene drive systems though not yet demonstrated, are also potentially highly invasive. 22 While the relationship of IIT and RIDL with the well-known SIT is clear, there are not such obvious analogies with current methods to guide the testing, deployment, and use of gene drive systems.…”

MGDrivE: A modular simulation framework for the spread of gene drives through spatially-explicit mosquito populations

“…At the time of publication, the MGDrivE package includes inheritance cubes for: a) standard Mendelian inheritance, b) homing-based drive intended for population replacement or suppression [26,27,29,30], c) Medea (a maternal toxin linked to a zygotic antidote) [31], d) other toxin-antidote-based underdominant systems such as UD MEL [13,15,32], e) reciprocal chromosomal translocations [14,33], f) Wolbachia [34], and g) the RIDL system [35] (release of insects carrying a dominant lethal gene). Details of each of these systems are provided in the S1 User Manual.…”

Gene Drive Strategies for Population Replacement

“…Semele is a single-locus system consisting of a toxin gene expressed in the semen of transgenic males that either kills or renders infertile wild-type females and an antidote gene expressed in females that protects them against the effects of the toxin [74]. The name is an acronym for "semen-based lethality" and, like Medea, also has Greek origins.…”

“…This happens because all of the wild females that mate with the Semele males are susceptible to their toxic semen. If both males and females carrying the Semele allele are released, the system displays bistable dynamics with a threshold frequency of B36% in the absence of fitness costs [74]. Above the threshold, the selective advantage of the female antidote outweighs the reproductive disadvantage conferred by the toxic semen and the system spreads into the population.…”