Figure 1.

Identification and Characterization of the Autosomal Component of the C. elegans X:A Sex Determination Signal

(A) Genetic hierarchy regulating sex determination and dosage compensation. The ratio of X chromosomes to sets of autosomes is the primary signal that determines sexual fate and the level of X chromosome gene expression. In XX diploids (2X:2A), xol-1 is repressed, permitting high expression of sdc-2, the pivotal XX-specific trigger of dosage compensation and hermaphrodite development. In XO diploids (1X:2A), xol-1 is active and sdc-2 is repressed, permitting male development. The dosage compensation machinery is inactive in males. A group of X-linked genes called X signal elements (XSEs) communicates X chromosome dose by repressing xol-1 when they are present in two doses but not in one dose. The autosomal signal must oppose the X signal, but prior to our current work, the nature of the autosomal signal was not known. A key question was whether a group of discrete, dosesensitive autosomal signal elements (ASEs) communicates autosomal dose in a manner analogous to XSEs.

(B) Predicted outcomes from changing the dose of X and autosomal signal elements in 2X:2A and 1X:2A animals. Mutations in X signal elements cause sex-specific, dose-dependent phenotypes. XX animals with xse mutations die from the disruption of dosage compensation, and the survivors are masculinized and dumpy (Dpy). Mutations in potential autosomal signal elements (ASEs) should also cause synergistic, dose-dependent phenotypes, but ones opposite to those caused by XSE mutations. Moreover, since the sex determination signal is the ratio of X chromosomes to autosomes, a decrease in the dose of ASEs in XX animals is predicted to compensate for a decrease in the dose of XSEs by restoring the overall balance of the perceived X:A signal. Conversely, an increase in the dose ASEs in XO animals should compensate for an increase in XSEs. Furthermore, an increase in the dose of ASEs in XX animals should enhance the mutant phenotype caused by a decrease in XSEs, and a decrease in the dose of ASEs in XO animals should enhance the mutant phenotype caused by an increase in XSEs. In the figure, a decrease in the dose of either XSEs or ASEs is represented by a downward arrow, and an increase in XSE or ASE dose is represented by an upward arrow. If the change in signal element dose is masculinizing, the arrow is aqua; if the change is feminizing, the arrow is fuchsia.

(C) Genetic screen for mutations in ASE genes. The viability of hermaphrodites doubly mutant for the XSEs fox-1 sex-1 depends on yEx483[Pdpy-30::sdc-2(+)], a mitotically unstable extrachromosomal array that overexpresses sdc-2(+) constitutively from a promoter insensitive to the X:A signal. This array, referred to as yEx[sdc-2(+)] in the figure, also carries the marker myo-2::gfp, which causes the pharynx to be green. Following mutagenesis with EMS, mutations that suppress fox-1 sex-1 lethality can be recovered from hermaphrodites that acquire the ability to live in the absence of the rescuing array and therefore do not have a green pharynx. These are candidate loss-of-function mutations in ASEs.