GENETIC AND MOLECULAR ANALYSIS OF THE AUTOSOMAL COMPONENT OF THE PRIMARY SEX DETERMINATION SIGNAL OF DROSOPHILA-MELANOGASTER

Drosophila sex is determined by the action of the X:A chromosome balan ce on transcription of Sex-lethal (Sxl), a feminizing switch gene. We obtained loss-of-function mutations in denominator elements of the X:A signal by selecting for dominant suppressors of a female-specific let hal mutation in the numerator element, sisterlessA (sisA). Ten suppres sors were recovered in this extensive genome-wide selection. All were mutations in deadpan (dpn), a pleiotropic locus previously discovered to be a denominator element. Detailed genetic and molecular characteri zation is presented of this diverse set of new dpn alleles including t heir effects on Sxl. Although selected only for impairment of sex-spec ific functions, all were also impaired in nonsex-specific functions. M ale-lethal effects were anticipated for mutations in a major denominat or element, but we found that viability of males lacking dpn function was reduced no more than 50% relative to their dpn(-) sisters. Moreove r, loss of dpn activity in males caused only a modest derepression of the Sxl ''establishment'' promoter (Sxl(Pe)), the X:A target. By itsel f, dpn cannot account for the masculinizing effect of increased autoso mal ploidy, the effect that gave rise to the concept of the X:A ratio; nevertheless, if there are other denominator elements, our results su ggest that their individual contributions to the sex-determination sig nal are even less than that of dpn. The time course of expression of d pn and of Sxl in dpn mutant backgrounds suggests that dpn is required for sex determination only during the later stages of X:A signaling in males to prevent inappropriate expression of Sxl(Pe) in the face of i ncreasing sis gene product levels.