EVIDENCE FOR EVOLUTIONARY CONSERVATION OF SEX-DETERMINING GENES

Most metazoans occur as two sexes. Surprisingly, molecular analyses ha ve hitherto indicated that sex-determining mechanisms differ completel y between phyla. Here we present evidence to the contrary, We have iso lated the male sexual regulatory gene mab-3 (ref. 1) from the nematode Caenorhabditis elegans and found that it is related to the Drosophila melanogaster sexual regulatory gene doublesex (dsx)(2). Both genes en code proteins with a DNA-binding motif(3) that we have named the 'DM d omain'. Both genes control sex-specific neuroblast differentiation and yolk protein gene transcription; dsx controls other sexually dimorphi c features as well, The form of DSX that is found in males can direct male-specific neuroblast differentiation in C. elegans. This structura l and functional similarity between phyla suggests a common evolutiona ry origin of at least some aspects of sexual regulation. We have ident ified a human gene, DMT1, that encodes a protein with a DM domain and find that DMT1 is expressed only in testis. DMT1 maps to the distal sh ort arm of chromosome 9, a location implicated in human XY sex reversa l(4). Proteins with DM domains may therefore also regulate sexual deve lopment in mammals.