THE C-ELEGANS SEX-DETERMINING GENE FEM-2 ENCODES A PUTATIVE PROTEIN PHOSPHATASE

The genetic and molecular analysis of genes involved in the regulation of sex determination in Caenorhabditis elegans suggests that the gene fem-2 plays an important role in regulating a pathway transducing a n on-cell-autonomous signal to a nuclear transcription factor. The wild- type fem-2 gene was cloned by identifying sequences from the C. elegan s physical map that could restore normal Fem-2 function to homozygous mutant fem-2 transgenic animals. cDNA sequences mapping to the minimal rescuing region correspond to an open reading frame with a sequence s imilar to protein phosphatase 2C enzymes from systems as diverse as ye ast, humans, and plants, but the alignments suggest that FEM-2 falls i nto a separate class of proteins than the canonical homologues. Severa l fem-2 mutant alleles were sequenced, and the mutations are predicted to cause protein changes consistent with their observed phenotypes, s uch as missense mutations in conditional alleles, and a nonsense mutat ion in a predicted null allele. This is the first evidence implicating phosphorylation and/or dephosphorylation as a control mechanism in C. elegans sex determination.