Nixconfers heritable sex-conversion inAedes aegyptiandmyo-sexis needed for male flight

A dominant and hemizygous male-determining locus (M locus) establishes the male sex (M/m) in the yellow fever mosquito,Aedes aegypti.Nixis a male-determining factor (M factor) in the M locus and its transient expression in females (m/m) results in partial masculinization. Here, we show that theNixtransgene alone was sufficient to convert females into fertile males, which continued to produce sex-converted progeny in subsequent generations. However, assisted mating with wild-type females was necessary, as the converted m/m males could not fly. Knockout ofmyo-sex, a myosin heavy chain gene and the only other protein-coding gene reported in the M locus, rendered wild-type males flightless. Thus,Nixalone converts femaleAe. aegyptito fertile males andmyo-sexis required for male flight. Only femaleAe. aegyptimosquitoes bite and transmit disease-causing viruses.Nix-mediated female-to-male conversion is 100% penetrant and stable over many generations, indicating great potential for mosquito control.