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Evidence for evolutionary conservation of sex-determining genes

Nature volume 391, pages 691–695 (1998)Cite this article

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.

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Figure 1: Isolation and characterization of the mab-3 gene.
Figure 2: Splicing pattern and mRNA expression of mab-3.
Figure 3: Male DSX, but not female DSX, can direct V-ray formation in Celegans.
Figure 4: DM domain proteins and DMT1.

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Acknowledgements

We thank colleagues at the University of Minnesota and MRC-LMB for discussions; M. de Bono for microinjection of cosmids from the mab-3 region and for discussion; K. Burtis for dsx cDNAs; A. Coulson, J. Sulston, S. Chissoe and the C. elegans Genome Sequencing Consortium for assistance with physical mapping and sequencing of the mab-3 region; C. Kenyon, C. Hunter and D.Cowing for the mab-3(mu15) allele; Y. Kohara for a mab-3 cDNA clone; M. Sanders for a human-tissue blot; E. Parker for technical support; and V. Bardwell, J. Heasman, H. Towle, B. Van Ness and C. Wylie for critical reading of the manuscript. Some of the work by M.M.S. was performed in the laboratory of I.Greenwald, whom we thank. This work was supported by grants from the Minnesota Medical Foundation, University of Minnesota Graduate School and the NIH to D.Z., by NSF predoctoral fellowships to C.E.S. and M.M.S., and by the MRC and the HHMI.

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Author notes

  1. Caroline E. Shamu

    Present address: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, 02115, USA

  2. Michael M. Shen

    Present address: Center for Advanced Biotechnology and Medicine, and Department of Pediatrics, UMDNJ-Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, New Jersey, 08854, USA

Authors and Affiliations

  1. Institute of Human Genetics and Department of Biochemistry,

    Christopher S. Raymond & David Zarkower

  2. Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, 55455, Minnesota, USA

    Kelly J. Seifert & Betsy Hirsch

  3. MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

    Caroline E. Shamu, Michael M. Shen & Jonathan Hodgkin

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  1. Christopher S. Raymond
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Correspondence to David Zarkower.

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Raymond, C., Shamu, C., Shen, M. et al. Evidence for evolutionary conservation of sex-determining genes. Nature 391, 691–695 (1998). https://doi.org/10.1038/35618

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