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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 domesticamale determiner(Mdmd), as the M-factor.Mdmdoriginated from a duplication of the spliceosomal factor geneCWC22(nucampholin). TargetedMdmddisruption results in complete sex reversal to fertile females because of a shift from male to female expression of the downstream genestransformeranddoublesexThe presence ofMdmdon different chromosomes indicates thatMdmdtranslocated 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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One cell. One organism. One fate: male, or female. The way Nature designs things, you would expect traits as fundamental as those that make a boy a boy or a girl a girl, for instance, to be inscribed in their respective DNA from the very start. In a way they...