Some proposed genetics-based vector control methods aim to suppress or eliminate a mosquito population in a similar manner to the sterile insect technique. One approach under development in
Anopheles
mosquitoes uses homing endonuclease genes (HEGs)—selfish genetic elements (inherited at greater than Mendelian rate) that can spread rapidly through a population even if they reduce fitness. HEGs have potential to drive introduced traits through a population without large-scale sustained releases. The population genetics of HEG-based systems has been established using discrete-time mathematical models. However, several ecologically important aspects remain unexplored. We formulate a new continuous-time (overlapping generations) combined population dynamic and genetic model and apply it to a HEG that targets and knocks out a gene that is important for survival. We explore the effects of density dependence ranging from undercompensating to overcompensating larval competition, occurring before or after HEG fitness effects, and consider differences in competitive effect between genotypes (wild-type, heterozygotes and HEG homozygotes). We show that population outcomes—elimination, suppression or loss of the HEG—depend crucially on the interaction between these ecological aspects and genetics, and explain how the HEG fitness properties, the homing rate (drive) and the insect's life-history parameters influence those outcomes.
Comprehensive computational design of mCreI homing endonuclease cleavage specificity for genome engineering