Comparing evolutionary changes that occurred in several independent lineages can help reveal their underlying mechanisms. Phylogenetic studies suggest that hermaphroditism evolved independently in the nematodes C. elegans and C. briggsae. In C. briggsae,
she-1 is a novel gene that promotes hermaphrodite spermatogenesis, since
she-1 mutants develop as male/female strains. To learn what genes interact with
she-1 to control hermaphroditic development, we isolated 5 recessive and 7 dominant suppressors.
Two of these suppressors might act with the Tip60/NuA4 Histone Acetyl-Transferase complex to regulate germ cell fates. First, the recessive mutation
v92 caused 81% synthetic lethality with
trr-1(RNAi), which targets the Tip60/NuA4 HAT complex. By contrast, we see almost no lethality in the single mutants. Furthermore,
v92 suppressed the feminization normally caused by
trr-1 in 7% of the surviving animals. We saw an even stronger interaction using RNAi against
mys-1, another component of the Tip60/NuA4 HAT complex. Although neither
trr-1 nor
mys-1 RNAi cause lethality on their own, completely inactivating this complex is lethal. Thus, we suspect that
v92 works with the Tip60 complex to carry out an essential function.
Second, the dominant mutation
v99 suppressed the feminization caused by
trr-1 in 3% of the animals, and suppressed that caused by
mys-1 in 32% of the animals. Although
v99 caused a low level of lethality on its own, it did not show synthetic lethality with
trr-1 or
mys-1. Thus, we suspect its activity might be limited to controlling germ cell fates.
To identify the genes these suppressors define, we are now cloning
v92 and
v99. By using SNPs, we have mapped
v92 to a 600 kb region on LGII, and are testing candidate genes. The
v99 mutation maps to a larger region on LGIII.