title: Evidence for evolutionary conservation of sex-determining genes.
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 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 motif 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 reversal. Proteins with DM domains may therefore also regulate sexual development in mammals.
authors.affiliation: Institute of Human Genetics, Department of Biochemistry, University of Minnesota Medical School, Minneapolis 55455, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Raymond
authors.forename: C E
authors.initials: CE
authors.lastname: Shamu
authors.forename: M M
authors.initials: MM
authors.lastname: Shen
authors.forename: K J
authors.initials: KJ
authors.lastname: Seifert
authors.forename: B
authors.initials: B
authors.lastname: Hirsch
authors.forename: J
authors.initials: J
authors.lastname: Hodgkin
authors.forename: D
authors.initials: D
authors.lastname: Zarkower
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics; D005260:Female; D015801:Helminth Proteins / Q000235:genetics; D006801:Humans; D019476:Insect Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000235:genetics; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D019849:Sex Determination Processes; D014157:Transcription Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; C110547:DMRT1 protein; D004268:DNA-Binding Proteins; C070369:DSX protein, Drosophila; D029721:Drosophila Proteins; D015801:Helminth Proteins; D019476:Insect Proteins; C110548:Mab-3 protein, C elegans; D008565:Membrane Proteins; D011506:Proteins; D011971:Receptors, Immunologic; C110546:TYROBP protein, human; D014157:Transcription Factors