The AalNix3&4 isoform is required and sufficient to convert Aedes albopictus females into males

Y. Zhao, B. Jin, P. Liu, X. Xiao, L. Cai, Z. Xie, L. Kong, T. Liu, W. Yang, Y. Wu, J. Gu, Z. Tu, A. A. James and X.-G. Chen,  PLOS Genetics,  18:e1010280. 2022.

Author summary Nix serves as a conserved male-determining factor in the two most important mosquito arboviral vectors, Ae. aegypti and Ae. albopictus. AaeNix alone can convert Ae. aegypti females into fertile but flightless males. AalNix has four alternative splice isoforms whereas AaeNix has one. Little was known previously about which AalNix isoform(s) serve as the primary signal for sex determination. We cloned the promoter region of AalNix gene and constructed piggybac-based AalNix overexpression constructs with different isoform variants. Following transformation and recovery of transgenic lines, we observed that expression of the AalNix3&4 isoform could shift the alternative splicing of the sex determination genes, doublesex and fruitless, from female to male isoforms, and phenotypically masculinize females or completely convert females into males. Importantly, the sex-converted pseudo-males are fertile and capable of flight. Thus, AalNix is the primary signal for male sex determination in Aedes albopictus and provides a basis for sex segregation and further Cas9-mediated gene-drive population suppression.

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