Leveraging sex determination systems for genetic biocontrol of dipteran pests

Genetic biocontrol is an increasingly important way to suppress insect pest populations and to mitigate their economic and health impact. One key advantage is that it is species-specific, as it relies on the mating of released males with wild females to either suppress or modify populations. The latter is through rendering females incompetent at disease transmission. Sex separation is critical to ensure the efficiency of these control programs, and it is essential in the case of vector control to avoid releasing females that can transmit pathogens. Modern genetic methods provide the opportunity to target or manipulate components of the sex determination systems to facilitate genetic biocontrol with new means to effectively accomplish sex-specific selection, lethality, or sterility. For example, sex-specific splicing elements in genes in the sex determination pathway are used to produce sex-specific markers. Sex-linked recessive lethal alleles are used to differentially eliminate the transgene-marked sex chromosome from males to produce nontransgenic males. Knocking out or knocking down sex-specific isoforms of genes in the sex determination pathway is employed to confer female-specific lethality or sterility. Sex determination pathways and sex chromosomes are also targeted for gene drives that suppress pest populations by introducing extreme sex ratio biases. Here, we review these and other recent advances in genetic technologies for pest control that have benefited from knowledge of sex determination systems in Diptera.