Conspecific and interspecific interactions between the FEM-2 and the FEM-3 sex-determining proteins despite rapid sequence divergence

J Mol Evol. 2006 Mar;62(3):281-91. doi: 10.1007/s00239-005-0084-5. Epub 2006 Feb 13.


Using degenerate oligonucleotide primers, we isolated the Caenorhabditis remanei orthologue of the C. elegans sex-determining phosphatase gene fem-2 as well as two other protein phosphatase homologues. Despite the significant sequence divergence between C. elegans and C. remanei FEM-2, we used RNAi-mediated gene knockdown to demonstrate that at least some aspects of male development require FEM-2 function in C. remanei. Consistent with this functional conservation, the conspecific interaction between the FEM-2 and the FEM-3 proteins observed in C. elegans also occurs in C. remanei. To further explore whether the rapid evolution of FEM-2 and FEM-3 affects their molecular interactions, we tested for cross-species interactions between the proteins from C. elegans, C. briggsae, and C. remanei. Although all FEM-2/FEM-3 pairs from a single species interact, only two out of six interspecific pairs bind each other, showing that FEM-2 and FEM-3 are coevolving. Both interspecific interactions involved C. briggsae FEM-3. We constructed chimeric versions of FEM-2 consisting of various combinations of the C. elegans and C. remanei proteins. C. briggsae FEM-3 interacted with all the chimeras, even those that did not interact with either C. elegans or C. remanei FEM-3. We hypothesize that the promiscuity of C. briggsae FEM-3 reflects an increased reliance on evolutionarily constrained regions of FEM-2 for binding. If so, our data support the notion that the coevolution of two interacting proteins sometimes involves a shift in the domains that contribute to binding.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis / genetics
  • Caenorhabditis / growth & development
  • Caenorhabditis / metabolism*
  • Caenorhabditis elegans Proteins
  • Conserved Sequence
  • Evolution, Molecular*
  • Helminth Proteins / chemistry*
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism*
  • Molecular Sequence Data
  • Phosphoprotein Phosphatases
  • Phylogeny
  • RNA Interference
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sex Determination Processes*
  • Time Factors


  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • fem-3 protein, C elegans
  • Fem-2 protein, C elegans
  • Phosphoprotein Phosphatases