A novel regulatory mutation in the C. elegans sex determination gene tra-2 defines a candidate ligand/receptor interaction site.

Sex determination in the nematode C. elegans is dependent on cell-to-cell communication, which appears to be mediated by the predicted membrane protein TRA-2A and the secreted protein HER-1. In XO males, HER-1 is hypothesised to function as a repressive ligand that inactivates the TRA-2A receptor. In XX animals, HER-1 is absent and TRA-2A promotes hermaphrodite development by negatively regulating the FEM proteins. This paper describes the molecular and genetic characterisation of a novel class of feminising mutations called tra-2(eg), for enhanced gain-of-function. In XX animals, mutant tra-2(eg) activity promotes entirely normal hermaphrodite development. However, the tra-2(eg) mutations generate an XO-specific gain-of-function phenotype, because they transform XO mutants from male into hermaphrodite. Therefore, the tra-2(eg) mutations identify a major regulatory site, which may be the TRA-2A/HER-1 interaction site. All ten tra-2(eg) mutations encode identical missense changes in a predicted extracellular domain of TRA-2A, named the EG site. It is proposed that the tra-2(eg) mutation encodes a TRA-2A protein that functions constitutively in XO animals, because it is defective in HER-1 binding. Phenotypic characterisation of sexually transformed XO tra-2(eg) hermaphrodites reveals that their fertility is strongly affected by dosage compensation mutations, suggesting that dosage compensation plays a role in normal gametogenesis.