Population dynamics of engineered underdominance and killer-rescue gene drives in the control of disease vectors

A number of different genetics-based vector control methods have been proposed. Two approaches currently under development in Aedes aegypti mosquitoes are the two-locus engineered underdominance and killer-rescue gene drive systems. Each of these is theoretically capable of increasing in frequency within a population, thus spreading associated desirable genetic traits. Thus they have gained attention for their potential to aid in the fight against various mosquito-vectored diseases. In the case of engineered underdominance, introduced transgenes are theoretically capable of persisting indefinitely (i.e. it is self-sustaining) whilst in the killer-rescue system the rescue component should initially increase in frequency (while the lethal component (killer) is common) before eventually declining (when the killer is rare) and being eliminated (i.e. it is temporally self-limiting). The population genetics of both systems have been explored using discrete generation mathematical models. The effects of various ecological factors on these two systems have also been considered using alternative modelling methodologies. Here we formulate and analyse new mathematical models combining the population dynamics and population genetics of these two classes of gene drive that incorporate ecological factors not previously studied and are simple enough to allow the effects of each to be disentangled. In particular, we focus on the potential effects that may be obtained as a result of differing ecological factors such as strengths of larval competition; numbers of breeding sites; and the relative fitness of transgenic mosquitoes compared with their wild-type counterparts. We also extend our models to consider population dynamics in two demes in order to explore the effects of dispersal between neighbouring populations on the outcome of UD and KR gene drive systems.Author summary: Vector-borne diseases represent a severe burden to both human and animal health worldwide. The methods currently being used to control a range of these diseases do not appear sufficient to address the issues at hand. As such, alternate methods for the control of vector-borne diseases are currently being investigated. Among the promising techniques currently being considered are a range of genetic control methods known as gene drive systems. These allow desirable genetic traits (such as a much reduced capacity for vectors to transmit viruses) to be spread through a target population; taking advantage of natural mate seeking behaviour to locate vector sub-populations that can be extremely difficult for humans to locate and reach. Here we use mathematical models (parameterised to consider mosquito populations) to demonstrate the robustness of the engineered underdominance and killer-rescue classes of gene drive to different ecological factors including birth and death rates; the number and quality of breeding sites (i.e. carrying capacity); and the strength of density-dependent competition during the larval development phase. We then go on to explore the range of potential outcomes that may result from the migration of individuals between two neighbouring populations.