Evidence for evolutionary conservation of sex-determining genes

Christopher S. Raymond, Caroline E. Shamu, Michael M. Shen, Kelly J. Seifert, Betsy Hirsch, Jonathan Hodgkin and David Zarkower ()
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Christopher S. Raymond: Institute of Human Genetics and Department of Biochemistry
Caroline E. Shamu: MRC Laboratory of Molecular Biology
Michael M. Shen: MRC Laboratory of Molecular Biology
Kelly J. Seifert: University of Minnesota Medical School
Betsy Hirsch: University of Minnesota Medical School
Jonathan Hodgkin: MRC Laboratory of Molecular Biology
David Zarkower: Institute of Human Genetics and Department of Biochemistry

Nature, 1998, vol. 391, issue 6668, 691-695

Abstract: 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.

Date: 1998
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DOI: 10.1038/35618

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