Homologs of the Caenorhabditis elegans masculinizing gene her-1 in C-briggsae and the filarial parasite Brugia malayi

The masculinizing gene her-1 in Caenorhabditis elegans (Ce-her-1) encodes a novel protein, HER-1A, which is required for male development. To identify conserved elements in her-1 we have cloned and characterized two homologou s nematode genes: one by synteny from the closely related free-living speci es C. briggsae (Cb-her-1) and the other, starting with a fortuitously ident ified expressed sequence tag, from the distantly related parasite Brugia ma layi (Bm-her-1). The overall sequence identities of the predicted gene prod ucts with Ce-HER-1A are only 57% for Cb-HER-1, which is considerably lower than has been found for most homologous briggsae genes, and 35% for Bm-HER- 1. However, conserved residues are found throughout both proteins, and like Ce-HER-1A, both have putative N-terminal signal sequences. Ce-her-1 produc es a larger masculinizing transcript (her-1a) and a smaller transcript of u nknown function (her-1b); both are present essentially only in males. By co ntrast, Cb-her-1 appears to produce only one transcript, corresponding to h er-1a; it is enriched in males but present also in hermaphrodites. Injectio n of dsRNA transcribed from Cb-her-1 into C briggsae hermaphrodites (RNA in terference) caused XO animals to develop into partially fertile hermaphrodi tes. Introducing a Cb-her-1 construct as a transgene under control of the C . elegans unc54 myosin heavy chain promoter caused strong masculinization o f both C briggsae and C. elegans hermaphrodites. Introduction of a similar Bm-her-1 construct into C. elegans caused only very weak, if any, masculini zation. We conclude that in spite of considerable divergence the Cb gene is likely to be a functional ortholog of Ce-her-1, while the function of the distantly related Bm gene remains uncertain.