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Male sex in houseflies is determined by Mdmd, a paralog of the generic splice factor gene CWC22

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Science  12 May 2017:
Vol. 356, Issue 6338, pp. 642-645
DOI: 10.1126/science.aam5498

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Disrupting housefly gene reverses sex

Sex comes in many forms, even when considered at the molecular level. In different animals, the chromosomes and specific genes that function in sex determination vary widely. As a case in point, the familiar housefly displays a highly variable sex determination system. In this animal, the male determiner (M-factor) instructs male development when it is active, but female development results when it is inactive. Sharma et al. now identify the housefly M-factor, which arose via the co-option of existing genes, gene duplication, and neofunctionalization. The findings elucidate the remarkable diversity in sex-determining pathways and the forces that drive this diversity.

Science, this issue p. 642

Abstract

Across species, animals have diverse sex determination pathways, each consisting of a hierarchical cascade of genes and its associated regulatory mechanism. Houseflies have a distinctive polymorphic sex determination system in which a dominant male determiner, the M-factor, can reside on any of the chromosomes. We identified a gene, Musca domestica male determiner (Mdmd), as the M-factor. Mdmd originated from a duplication of the spliceosomal factor gene CWC22 (nucampholin). Targeted Mdmd disruption results in complete sex reversal to fertile females because of a shift from male to female expression of the downstream genes transformer and doublesex. The presence of Mdmd on different chromosomes indicates that Mdmd translocated to different genomic sites. Thus, an instructive signal in sex determination can arise by duplication and neofunctionalization of an essential splicing regulator.

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