The primary signal for sex determination in C. elegans is the ratio of X chromosomes to sets of autosomes (the X:A ratio), which controls the expression of the developmental switch gene
xol-1. High levels of
xol-1 expression promote male development, and low levels promote hermaphrodite development.
xol-1 also regulates the dosage compensation process, which reduces gene expression from both hermaphrodite X chromosomes to equal that from the male X. An embryo cannot afford to assess its X:A ratio incorrectly, since setting the inappropriate level of X chromosome expression can be lethal to either sex. Studies of duplications and deficiencies have shown that a few discrete regions of X are counted as part of the signal. Duplications of X signal elements in XO embryos increase the X:A ratio and decrease
xol-1 expression to lethal levels. Likewise, deficiencies of signal elements in XX embryos increase
xol-1 levels, and thereby cause defects from elevated X-chromosome expression. Two copies of the duplication yDp14 are 100% lethal to XO animals. A putative null mutation of a known signal element,
fox-1(
y303), only very weakly suppresses this XO-specific lethality, but may reduce the X:A ratio so that mutations that eliminate one further signal element will suppress this lethality. Based on this assumption, we are conducting a genetic screen to identify signal elements by screening for suppressors of the male lethality of yDp14;
y303. At least six X-linked suppressors have been isolated, all of which complement the known sex determination genes on X. Four of these suppressors have hermaphrodite-specific defects in the absence of yDp14, suggesting that they are good candidates for signal element mutations.