Sex and the singular DM domain: insights into sexual regulation, evolution and plasticity

Abstract

Most animals reproduce sexually and thus require a sex-determining mechanism. Sex-determining mechanisms are surprisingly diverse among animal species, and genes at the top of sex-determining pathways rapidly turn over during evolution. Genes containing the DM domain DNA-binding motif appear to have an ancient and conserved role in controlling sexual differentiation and sex determination. Invertebrate DM domain genes integrate spatial and temporal inputs with sex-determining pathways to coordinate the sexual differentiation of diverse structures. Studies of the DM domain gene doublesex in Drosophila melanogaster are revealing how new sexually dimorphic features evolve. In vertebrates, the DM domain gene Dmrt1 is required for testicular development. In several non-mammalian vertebrates (that is, birds, fish and amphibians) Dmrt1 or a close homologue has acquired control of sex determination during evolution. Detailed studies in the mouse reveal that Dmrt1 has diverse functions in gonadal development, including a role in preventing male-to-female transdifferentiation of testis cells.