Although no MAGE homologous sequences have been identified in Caenorhabditis elegans, Saccharomyces cerevisiae or Schizosaccharomyces pombe, MAGE sequences have been found in several vegetal species, including Arabidopsis thaliana. A database screening was performed to identify all of the recorded members of both classes of human MAGE genes. This report provided an overview of the MAGE family and proposed a general nomenclature for all of the MAGE genes identified thus far. The MAGE-D genes were particularly well conserved between man and mouse, suggesting that they exert important functions. In addition, the genomic structure of the MAGE-D genes indicates that one of them corresponds to the founder member of the family, and that all of the other MAGE genes are retrogenes derived from that common ancestral gene. MAGE-A1 belongs to a group of germline-specific genes that rely primarily on DNA methylation for repression in somatic tissues. In many types of tumors, the promoter of these genes becomes demethylated and transcription becomes activated. MAGE-A1 acts as a transcriptional repressor. MAGE -A1, the first characterized cancer-germline gene, belongs to a family of twelve genes located on the X chromosome in region q28 (5,6).
Genes of the MAGE family have their entire coding sequences located in the last exon, which shows 64 to 85% identity with that of MAGE 1 (De Plaen et al., 1994). (An exception is MAGE D2, 300470). The coding sequences predict the main structural features of all MAGE proteins, in contrast, the promoters and first exons of the MAGE genes show considerable variability, possibly enabling the same function to be expressed under different transcriptional controls. In their annotation of the DNA sequence of the human X chromosome and the predicted proteome, Ross et al. (2005) noted that the MAGE domain was present in 32 genes. In comparison, only 4 other MAGE genes had been reported in the rest of the genome: MAGE F1 (609267) on chromosome 3, and MAGE L2 (605283), NDN (602117), and NDNL2 (608243) in the proximal portion of the long arm of chromosome 15. The MAGE gene products are members of the cancer-testis (CT) antigen group, which are characterized by their expression in a number of cancer types, while their expression in normal tissues is solely or predominantly in testis. This expression profile had led to the suggestion that the CT antigens are potential targets for tumor immunotherapy. Ross et al. (2005) stated that the X chromosome gene set they described contained 99 CT antigen genes, including novel members of the MAGE, GAGE, SSX, LAGE, CSAGE, and NXF families. Ross et al. (2005) predicted that approximately 10% of the genes on the X chromosome are of the CT antigen type. The remarkable enrichment for CT antigen genes on this chromosome relative to the rest of the genome may be indicative of a male advantage associated with these genes. Recessive alleles that are beneficial to males are expected to become fixed more rapidly on the X chromosome than on an autosome. If these alleles are detrimental to females, their expression could become restricted to male tissues as they rise to fixation. The CT antigen genes on the X chromosome are also notable for the expansion of various gene families by duplication. This degree of duplication is perhaps an indication of selection in males for increased copy number. In this