Tracing the origin of the compensasome: Evolutionary history of DEAH helicase and MYST acetyltransferase gene families

Dosage compensation in Drosophila is mediated by a complex of proteins and RNAs called the "compensasome." Two of the genes that encode proteins of th e complex, maleless (mle) and males-absent-on-the-first (mof), respectively , belong to the DEAH helicase and MYST acetyltransferase gene families. We performed comprehensive phylogenetic and structural analyses to determine t he evolutionary histories of these two gene families and thus to better und erstand the origin of the compensasome. All of the members of the DEAH and MYST families of the completely sequenced Saccharomyces cerevisiae and Caen orhabditis elegans genomes, as well as those so far (June 2000) found in Dr osophila melanogaster (for which the euchromatic part of the genome has als o been fully sequenced) and Homo sapiens, were analyzed. We describe a tota l of 39 DEAH helicases in these four species. Almost all of them can be gro uped in just three main branches. The first branch includes the yeast PRP2, PRP16, PRP22, and PRP43 splicing factors and their orthologs in animal spe cies. Each PRP gene has a single ortholog in metazoans. The second branch i ncludes just four genes, found in yeast (Ecm16) and Drosophila (kurz) and t heir orthologs in humans and Caenorhabditis. The third branch includes (1) a single yeast gene (YLR419w); (2) six Drosophila genes, including maleless and spindle-E/homeless; (3) four human genes, among them the ortholog of m aleless, which encodes RNA helicase A; and (4) three C. elegans genes, incl uding orthologs of maleless and spindle-E. Thus, this branch has largely ex panded in metazoans. We also show that, for the whole DEAH family, only MLE and its metazoan orthologs have acquired new protein domains since the fun gi/animals split. We found a total of 17 MYST family proteins in the four a nalyzed species. We determined putative orthologs of mof in both C. elegans and H. sapiens, and we show that the most likely ortholog in yeast is the Sas2 gene. Moreover, a paralog of mof exists in Drosophila. All of these re sults, together with those found for a third member of the compensasome, ms l-3, suggest that this complex emerged after the fungi/animals split and th at it may be present in mammalian species. Both gene duplication and the ac quisition of new protein modules may have played important roles in the ori gin of the compensasome.