Intraspecific variation in fem-3 and tra-2, two rapidly coevolving nematode sex-determining genes

Gene. 2005 Apr 11;349:35-42. doi: 10.1016/j.gene.2004.12.051.


The sex determination gene fem-3 encodes one of the most divergent proteins yet described in the terrestrial nematode Caenorhabditis. Despite this rapid sequence change, however, FEM-3 is essential for male development in the three species surveyed thus far. It also participates in conserved protein-protein complexes with the transmembrane receptor TRA-2 and the phosphatase FEM-2 in these species. These interactions show strong species specificity, indicating that conserved residues are not sufficient for function and that compensatory evolution between binding partners is important. To shed further light on the nature of this coevolution, and to discern the extent of amino acid polymorphism allowed in FEM-3 and the domain of TRA-2 that binds it, we have examined intraspecific variation in the gonochoristic species Caenorhabditis remanei. Ten new complete Cr-fem-3 alleles from three regions of the United States are described. We also obtained sequences for the FEM-3-binding domain of TRA-2 for 9 of the same strains. These alleles were compared with each other, with the European founder alleles, and with the orthologous sequences from the congeners Caenorhabditis elegans and C. briggsae. We find that FEM-3 harbors abundant amino acid polymorphisms along its entire length. The majority (but not all) of these occur in nonconserved residues, and in at least one domain there is evidence for diversifying selection. The FEM-3-binding domain of TRA-2 is less polymorphic than FEM-3. Amino acids neither polymorphic nor conserved between species are candidates for residues mediating species-specific interaction of FEM-3 with its binding partners.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Evolution*
  • Caenorhabditis / genetics
  • Conserved Sequence
  • Genes, Helminth*
  • Genes, T-Cell Receptor alpha
  • Genetic Variation*
  • Haplotypes
  • Helminth Proteins / chemistry
  • Helminth Proteins / genetics*
  • Male
  • Molecular Sequence Data
  • Phosphoprotein Phosphatases / genetics
  • Polymorphism, Genetic
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Sex Determination Processes*
  • Species Specificity


  • Helminth Proteins
  • Phosphoprotein Phosphatases