A male-determining factor in the mosquito Aedes aegypti

Abstract

Sex determination in the mosquito Aedes aegypti is governed by a dominant male-determining factor (M factor) located within a Y chromosome–like region called the M locus. Here, we show that an M-locus gene, Nix, functions as an M factor in A. aegypti. Nix exhibits persistent M linkage and early embryonic expression, two characteristics required of an M factor. Nix knockout with clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 resulted in largely feminized genetic males and the production of female isoforms of two key regulators of sexual differentiation: doublesex and fruitless. Ectopic expression of Nix resulted in genetic females with nearly complete male genitalia. Thus, Nix is both required and sufficient to initiate male development. This study provides a foundation for mosquito control strategies that convert female mosquitoes into harmless males.

The sex locus is tightly linked to factors conferring sex-specific lethal effects in the mosquito Aedes aegypti

“…Similar mechanisms of lethality are rather unlikely to be behind the phenomena described here, because dosage compensation appears not to exist in A. aegypti (Hall et al, 2015). Similarly, abnormalities in chromosomal transmission caused by transgenelinked inversions (cf.…”

“…However, myo-sex can be transferred together with the J2 transgene onto the m-chromosome through recombination, and thus it is not located within the SDR. Fluorescence in situ hybridization to mitotic chromosome spreads showed that in double recombinant males the hybridization signal from the transgenes practically colocalizes with the signal from Nix and myo-sex (Hall et al, 2014(Hall et al, , 2015. An estimated resolution of fluorescence in situ hybridization probe mapping to mitotic chromosomes (Timoshevskiy et al, 2013) indicates that the SDR may be o1 Mb.…”

“…In Culex and Aedes, chromosome 1 is sex determining; its p and q arms are largely syntenic to, respectively, the X chromosome and chromosomal arm 2R of Anopheles gambiae (Nene et al, 2007;Arensburger et al, 2010). In Aedes aegypti males, one chromosome of the chromosome 1 pair (hereafter called the M-chromosome, as opposed to the non-sex-specific m-chromosome) carries the SDR that does not recombine and harbors a dominant male-determining gene Nix (Hall et al, 2015). Thus, similar to 1 anophelines, the A. aegypti males are heterogametic (Mm) and females homogametic (mm).…”

Current status of genome editing in vector mosquitoes: A review

“…Another report in the same year by Hall et al demonstrated that knockout of male determining (Nix) gene has resulted in feminized genetic males with successful application of CRISPR/Cas9-mediated gene editing system (51). Further, their investigation on ectopic expression of Nix gene in genetic females confirmed that Nix is sufficient to initiate male development and thus has given a path to convert the female mosquitoes into harmless male (51).…”

“…Further, their investigation on ectopic expression of Nix gene in genetic females confirmed that Nix is sufficient to initiate male development and thus has given a path to convert the female mosquitoes into harmless male (51). This study may offer the possibilities of utilizing CRISPR/Cas9 for the customized editing of vector carrying female mosquito genomes.…”