| PubMed Abstract |
In Drosophila melanogaster, somatic sexual differentiation is regulated by a well characterized genetic hierarchy, by which
the ratio of X chromosomes to autosomes (X:A) ultimately directs the deployment of sex-specific transcription factors encoded
by doublesex (dsx) and fruitless (fru). In other dipterans, the X:A ratio is not the primary sex-determination signal. Correspondingly,
the Drosophila hierarchy is not fully conserved. In all non-drosophilid fly species examined, Sex-lethal (Sxl), the master
switch at the top of the Drosophila hierarchy, does not control somatic sex. This rapid divergence contrasts with the apparently
deep conservation of dsx, which in Drosophila controls virtually all aspects of somatic sex except for male courtship behavior
(which is controlled by fru). Sex-specific dsx mRNAs have been reported in Diptera, Lepidoptera and Hymenoptera, and dsx homologs
in nematodes and mammals are required for aspects of male differentiation. Thus, it seems that the bottom of the hierarchy
is rather ancient, especially compared with the top. To test this, we cloned insect and vertebrate homologs of the Drosophila
gene intersex (ix), which functions together with dsx at the bottom of the hierarchy in females. When expressed in D. melanogaster
females mutant at the endogenous ix gene, dipteran and lepidopteran ix homologs restore proper sexual differentiation, substantiating
the hypothesis that ix, like dsx, is broadly conserved. When the mouse homolog is expressed it produces a dominant-negative
phenotype suggesting partial functional divergence. Our results raise the possibility that a functional association between
ix- and dsx-related gene products existed before the origin of the bifunctional dsx gene used in insect sex determination.
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