A FAMILY OF RAPIDLY EVOLVING GENES FROM THE SEX REVERSAL CRITICAL REGION IN XP21

Patients with an intact SRY gene and duplications of portions of Xp21 develop as phenotypic females. We have recently mapped this sex reversal locus, DSS, to a 160-kb region of Xp21 that includes the adrenal hypoplasia congenita locus. To clone the gene(s) underlying DSS and AHC, we isolated expressed sequences from the region. Here we describe the characterization of two related genes. DAM10 and DAM6, expressed in adult testis and lung tumors. The predicted DAM10 and DAM6 proteins are 66% identical and are both highly similar to the MAGE family of tumor-associated antigens and to mouse necdin. Genes belonging to the MAGE superfamily, DAMs, MAGEs, and necdin, are likely to have originated from a common ancestor and to be subject to an unusually rapid evolution. The tumor-restricted expression of DAM proteins and their structural similarity to MAGE genes suggest that DAM peptides may be targets for active immunotherapy in lung cancer patients.