DoublesexMAB3related

Doublesex/MAB3-related (DMRT) genes constitute a conserved family of transcription factors defined by the DM domain, a DNA-binding motif shared across metazoans. The name reflects two well-studied members, the Drosophila doublesex (dsx) gene and the Caenorhabditis elegans mab-3 gene, but the family includes multiple orthologs in diverse species. They are typically encoded by a suite of genes with varying numbers of family members across taxa and are characterized by a shared DM domain that mediates DNA binding and transcriptional regulation.

DMRT genes play prominent roles in sexual development and differentiation. In insects, dsx functions through sex-specific alternative splicing to produce male- or female-specific protein isoforms that direct sexually dimorphic trait formation. In nematodes, mab-3 promotes male development and influences the expression of male-specific features. In vertebrates, DMRT family members are expressed in the gonads and other tissues where they contribute to gonad formation, germ cell development, and sexual differentiation; DMRT1 is among the best characterized and is implicated in testis development and maintenance in many species. Other vertebrate members, such as DMRT2, DMRT3, DMRT4, and DMRT5, have roles in development and tissue specification, including neural circuits that influence behavior in some mammals.

Mechanistically, DMRT proteins function as transcription factors that regulate downstream target genes relevant to sex differentiation and development. The evolutionary conservation of the DMRT family underscores the deep homology of sex-determining pathways across animals, even as specific regulatory networks and phenotypic outcomes show substantial diversification. Mutations or dysregulation of DMRT genes can be associated with disorders of sexual development in humans and other organisms, highlighting their biological and medical significance.