Evidence for evolutionary conservation of sex-determining genes

Nature. 1998 Feb 12;391(6668):691-5. doi: 10.1038/35618.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Biological Evolution*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 9
  • DNA-Binding Proteins / genetics
  • Drosophila Proteins*
  • Drosophila melanogaster / genetics
  • Female
  • Helminth Proteins / genetics
  • Humans
  • Insect Proteins / genetics
  • Male
  • Membrane Proteins
  • Molecular Sequence Data
  • Mutation
  • Proteins / genetics
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Sequence Homology, Amino Acid
  • Sex Determination Processes*
  • Transcription Factors*


  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • DMRT1 protein
  • DNA-Binding Proteins
  • DSX protein, Drosophila
  • Drosophila Proteins
  • Helminth Proteins
  • Insect Proteins
  • Mab-3 protein, C elegans
  • Membrane Proteins
  • Proteins
  • Receptors, Immunologic
  • TYROBP protein, human
  • Transcription Factors

Associated data

  • GENBANK/AF022388