Abstract
Engineered underdominance is one of a number of different gene drive strategies that have been proposed for the genetic control of insect vectors of disease. Here we model a two-locus engineered underdominance based gene drive system that is based on the concept of mutually suppressing lethals. In such a system two genetic constructs are introduced, each possessing a lethal element and a suppressor of the lethal at the other locus. Specifically, we formulate and analyse a population genetics model of this system to assess when different combinations of release strategies (i.e. single or multiple releases of both sexes or males only) and genetic systems (i.e. bisex lethal or female-specific lethal elements and different strengths of suppressors) will give population replacement or fail to do so. We anticipate that results presented here will inform the future design of engineered underdominance gene drive systems as well as providing a point of reference regarding release strategies for those looking to test such a system. Our discussion is framed in the context of genetic control of insect vectors of disease. One of several serious threats in this context are Aedes aegypti mosquitoes as they are the primary vectors of dengue viruses. However, results are also applicable to Ae. aegypti as vectors of Zika, yellow fever and chikungunya viruses and also to the control of a number of other insect species and thereby of insect-vectored pathogens.
Highlights
Aedes aegypti mosquitoes are the primary vector of dengue viruses (World Health Organization, 2016a)
We present a population genetics model describing the twolocus engineered underdominance based gene drive system shown in Fig. 1
This yields similar predictions to previous theoretical work in terms of introduction thresholds that give lasting transgene introgression from a single release ( ∼ 1/3 of the wild population for a system with strongly suppressed lethals and no fitness costs) (Davis et al, 2001). We utilised this model to study different release strategies; lethal genes; and strengths of lethal suppression. This revealed that for all genetic systems considered here it is possible to devise a release strategy that would give lasting transgene introgression so long as fitness costs fall into a tolerable range
Summary
Aedes aegypti mosquitoes are the primary vector of dengue viruses (World Health Organization, 2016a). Previous theoretical work on engineered underdominance systems (Buchman et al, 2016; Davis et al, 2001; Magori and Gould, 2006; Marshall and Hay, 2012) has focused on the case whereby transgenic individuals of both sexes are released into the wild population; carry lethals that affect both sexes; and display full suppression of one or two copies of a given lethal depending upon the number of copies of the relevant lethal suppressor possessed Whilst these assumptions are reasonable, there are a number of other possible release strategies (number, size and sex of releases) and genetic systems (sex specificity of lethals and strengths of lethal suppression) that are yet to be considered. It is anticipated that this study will inform future work seeking to develop engineered underdominance gene drive systems and be of interest to those planning to test a particular system/strategy ready for deployment in the field
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