Origin and evolution of the regulatory gene male-specific lethal-3.

Dosage compensation in Drosophila is mediated by genes known as "male-specific lethals" (msls). Several msls, including male-specific lethal-3 (msl-3), encode proteins of unknown function. We cloned the Drosophila virilis msl-3 gene. Using the information provided by the sequences of the Drosophila melanogaster and D. virilis genes, we found that sequences of other species can be aligned along their entire lengths with msl-3. Among them, there are genes in yeasts (the Schizosaccharomyces pombe Alp13 gene, as well as a putative Alp13 homolog, found in Saccharomyces cerevisae) and in mammals (MRG15 and MSL3L1 and their relatives) plus uncharacterized sequences of the nematode Caenorhabditis elegans and the plants Arabidopsis thaliana, Lycopersicon esculentum, and Zea mays. A second Drosophila gene of this family has also been found. It is thus likely that msl-3-like genes are present in all eukaryotes. Phylogenetic analyses suggest that msl-3 is orthologous to the mammalian MSL3L1 genes, while the second Drosophila melanogaster gene (which we have called Dm MRG15) is orthologous to mammalian MRG15. These analyses also suggest that the msl-3/MRG15 duplication occurred after the fungus/animal split, while an independent duplication occurred in plants. The proteins encoded by these genes have similar structures, including a putative chromodomain close to their N-terminal end and a putative leucine zipper at their C-terminus. The possible functional roles of these proteins are discussed.