Evolution of the PP2C family in Caenorhabditis: rapid divergence of the sex-determining protein FEM-2

J Mol Evol. 2002 Feb;54(2):267-82. doi: 10.1007/s0023901-0008-y.


To investigate the causes and functional significance of rapid sex-determining protein evolution we compared three Caenorhabditis elegans genes encoding members of the protein phosphatase 2C (PP2C) family with their orthologs from another Caenorhabditis species (strain CB5161). One of the genes encodes FEM-2, a sex-determining protein, while the others have no known sex-determining role. FEM-2's PP2C domain was found to be more diverged than the other PP2C domains, supporting the notion that sex-determining proteins are subjected to selective pressures that allow for or cause rapid divergence. Comparison of the positions of amino acid substitutions in FEM-2 with a solved three-dimensional structure suggests that the catalytic face of the protein is highly conserved among C. elegans, CB5161, and another closely related species C. briggsae. However, the non-conserved regions of FEM-2 cannot be said to lack functional importance, since fem-2 transgenes from the other species were unable to rescue the germ-line defect caused by a C. elegans fem-2 mutation. To test whether fem-2 functions as a sex-determining gene in the other Caenorhabditis species we used RNA-mediated interference (RNAi). fem-2 (RNAi) in C. elegans and C. briggsae caused germ-line feminization, but had no noticeable effect in CB5161. Thus the function of fem-2 in CB5161 remains uncertain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis / enzymology*
  • Caenorhabditis / genetics*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Catalytic Domain
  • Conserved Sequence
  • Disorders of Sex Development / genetics
  • Evolution, Molecular*
  • Gene Expression Regulation, Enzymologic
  • Genetic Variation*
  • Genome / genetics
  • Germ Cells
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation / genetics
  • Phosphoprotein Phosphatases / chemistry
  • Phosphoprotein Phosphatases / genetics*
  • Phosphoprotein Phosphatases / metabolism
  • Protein Phosphatase 2C
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Restriction Mapping
  • Sequence Alignment
  • Sex Determination Processes*
  • Zebrafish / genetics


  • Caenorhabditis elegans Proteins
  • RNA, Messenger
  • Fem-2 protein, C elegans
  • PPM1A protein, human
  • PPM1B protein, human
  • PPM1G protein, human
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2C