The mouse <i>Sry</i> locus harbors a cryptic exon that is essential for male sex determination.

Abstract

The mammalian sex-determining gene <i>Sry</i> induces male development. Since its discovery 30 years ago, <i>Sry</i> has been believed to be a single-exon gene. Here, we identified a cryptic second exon of mouse <i>Sry</i> and a corresponding two-exon type <i>Sry</i> (<i>Sry-T</i>) transcript. XY mice lacking <i>Sry-T</i> were sex-reversed, and ectopic expression of <i>Sry-T</i> in XX mice induced male development. <i>Sry-T</i> messenger RNA is expressed similarly to that of canonical single-exon type <i>Sry</i> (<i>Sry-S</i>), but SRY-T protein is expressed predominantly because of the absence of a degron in the C terminus of SRY-S. <i>Sry</i> exon2 appears to have evolved recently in mice through acquisition of a retrotransposon-derived coding sequence to replace the degron. Our findings suggest that in nature, SRY-T, not SRY-S, is the bona fide testis-determining factor.