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

Dosage compensation in Drosophila is mediated by genes known as "male-speci fic 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 ar e genes in yeasts (the Schizosaccharomyces pombe Alp13 gene, as well as a p utative Alp13 homolog, found in Saccharomyces cerevisae) and in mammals (MR G15 and MSL3L1 and their relatives) plus uncharacterized sequences of the n ematode Caenorhabditis elegans and the plants Arabidopsis thaliana, Lycoper sicon 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 al l eukaryotes. Phylogenetic analyses suggest that msl-3 is orthologous to th e mammalian MSL3L1 genes, while the second Drosophila melanogaster gene (wh ich we have called Dm MRG15) is orthologous to mammalian MRG15. These analy ses also suggest that the msl-3/MRG15 duplication occurred after the fungus /animal split, while an independent duplication occurred in plants. The pro teins 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 an discu ssed.