Nix alone is sufficient to convert female Aedes aegypti into fertile males and myo-sex is needed for male flight
Nix alone is sufficient to convert female Aedes aegypti into fertile males and myo-sex is needed for male flight
Tags: Aedes, Fruit fly, Gene drive synthetic, Genetic biocontrol, Population suppression, Sterile insect technique (SIT), Y-chromosomeA. Aryan, M. A. E. Anderson, J. K. Biedler, Y. M. Qi, J. M. Overcash, A. N. Naumenko, M. V. Sharakhova, C. H. Mao, Z. N. Adelman and Z. J. Tu, Proceedings of the National Academy of Sciences of the United States of America, 117:17702-17709. 2020.
A dominant male-determining locus (M-locus) establishes the male sex (M/m) in the yellow fever mosquito, Aedes aegypti. Nix, a gene in the M-locus, was shown to be a male-determining factor (M factor) as somatic knockout of Nix led to feminized males (M/m) while transient expression of Nix resulted in partially masculin-ized females (m/m), with male reproductive organs but retained female antennae. It was not clear whether any of the other 29 genes in the 1.3-Mb M-locus are also needed for complete sex -conversion. Here, we report the generation of multiple transgenic lines that express Nix under the control of its own promoter. Ge-netic and molecular analyses of these lines provided insights un-attainable from previous transient experiments. We show that the Nix transgene alone, in the absence of the M-locus, was sufficient to convert females into males with all male-specific sexually dimorphic features and male-like gene expression. The converted m/m males are flightless, unable to perform the nuptial flight required for mat-ing. However, they were able to father sex-converted progeny when presented with cold-anesthetized wild-type females. We show that myo-sex, a myosin heavy-chain gene also in the M-locus, was re-quired for male flight as knockout of myo-sex rendered wild-type males flightless. We also show that Nix-mediated female-to-male conversion was 100% penetrant and stable over many genera-tions. Therefore, Nix has great potential for developing mosquito control strategies to reduce vector populations by female-to-male sex conversion, or to aid in a sterile insect technique that requires releasing only non-biting males.