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

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, <i>Musca domestica</i><i>male determiner</i> (<i>Mdmd</i>), as the M-factor. <i>Mdmd</i> originated from a duplication of the spliceosomal factor gene <i>CWC22</i> (<i>nucampholin</i>). Targeted <i>Mdmd</i> disruption results in complete sex reversal to fertile females because of a shift from male to female expression of the downstream genes <i>transformer</i> and <i>doublesex</i> The presence of <i>Mdmd</i> on different chromosomes indicates that <i>Mdmd</i> translocated to different genomic sites. Thus, an instructive signal in sex determination can arise by duplication and neofunctionalization of an essential splicing regulator.