PT  - JOURNAL ARTICLE
AU  - Sharma, Akash
AU  - Heinze, Svenia D.
AU  - Wu, Yanli
AU  - Kohlbrenner, Tea
AU  - Morilla, Ian
AU  - Brunner, Claudia
AU  - Wimmer, Ernst A.
AU  - van de Zande, Louis
AU  - Robinson, Mark D.
AU  - Beukeboom, Leo W.
AU  - Bopp, Daniel
TI  - Male sex in houseflies is determined by <em>Mdmd</em>, a paralog of the generic splice factor gene <em>CWC22</em>
AID  - 10.1126/science.aam5498
DP  - 2017 May 12
TA  - Science
PG  - 642--645
VI  - 356
IP  - 6338
4099  - http://science.sciencemag.org/content/356/6338/642.short
4100  - http://science.sciencemag.org/content/356/6338/642.full
SO  - Science2017 May 12; 356
AB  - 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. 642Across 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.