1. Institute of Human Genetics and Department of Biochemistry
2. Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
3. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
4. Present addresses: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA (C.E.S.); Center for Advanced Biotechnology and Medicine, and Department of Pediatrics, UMDNJ-Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, New Jersey 08854, USA (M.M.S.).

Correspondence to: David Zarkower¹ Correspondence and requests for materials should be addressed to D.Z. (e-mail: Email: zarkower@gene.med.umn.edu).GenbankEmail: accessionnumberofthemab-3 genomic sequence is AF022388.

Abstract

Most metazoans occur as two sexes. Surprisingly, molecular analyses have hitherto indicated that sex-determining mechanisms differ completely between phyla. Here we present evidence to the contrary. We have isolated 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 encode proteins with a DNA-binding motif³ that we have named the 'DM domain'. Both genes control sex-specific neuroblast differentiation and yolk protein gene transcription; dsx controls other sexually dimorphic features as well. The form of DSX that is found in males can direct male-specific neuroblast differentiation in C. elegans. This structural and functional similarity between phyla suggests a common evolutionary origin of at least some aspects of sexual regulation. We have identified 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 short arm of chromosome 9, a location implicated in human XY sex reversal⁴. Proteins with DM domains may therefore also regulate sexual development in mammals.