Genomic organization and expression of the doublesex-related gene cluster in vertebrates and detection of putative regulatory regions for DMRT1

Genes related to the Drosophila melanogaster doublesex and Caenorhabditis e legans mab-3 genes are conserved in human. They are identified by a DNA-bin ding homology motif, the DM domain, and constitute a gene family (DMRTs). U nlike the invertebrate genes, whose role in the sex-determination process i s essentially understood, the function of the different vertebrate DMRT gen es is not as clear. Evidence has accumulated for the involvement of DMRT1 i n male sex determination and differentiation. DMRT2 (known as terra in zebr afish) seems to be a critical factor for somitogenesis. To contribute to a better understanding of the function of this important gene family, we have analyzed DMRT1, DMRT2, and DMRT3 from the genome model organism Digit rubr ipes and the medakafish, a complementary model organism for genetics and fu nctional studies. We found conservation of synteny of human chromosome 9 in F. rubripes and an identical gene cluster organization of the DMRTs in bot h fish. Although expression analysis and gene linkage mapping in medaka exc lude a function for any of the three genes in the primary step of male sex determination, comparison of F. rubripes and human sequences uncovered thre e putative regulatory regions that might have a role in more downstream eve nts of sex determination and human XY sex reversal.