Rapid Evolution and Divergence of Type II MAGE Genes in Eutherians

Melanoma-associated antigens (MAGE) are a group of more than 50 proteins that are produced in cancer cells and testis, as well as a dozen proteins expressed in normal tissues (type II MAGE genes). These genes are heterogeneous in their gene and protein structures and located in different chromosomes but are all expressed in normal tissues and not related to cancer. Our analysis showed that MAGE genes in non-mammals and monotremata are present in a single copy, two in metatherians and are a diverse group in all eutherians. Synteny conservation shows MAGED2 as the ancestral of all the genes in the family, and the most likely evolutionary history of the eutherian type-II MAGE genes based on their phylogenetic relations, genome location, homology conservation and the protein and gene structures is proposed here. Type II genes can be divided into two: those with 13 exons (MAGED1, MAGED2, TRO and MAGED4) and those with only one exon (MAGEE1, MAGEE2, MAGEF1, NDNL2, MAGEH1, MAGEL2 and NDN), which show a different evolutionary pattern. The use of genes of the type-II MAGE family as evolutionary markers, which have diverged early in the history of Eutherians, can better resolve the phylogenetic relationships among the poorly evolved mammalian clades such as Euarchontoglires, Laurasitheria (within Boreoeutheria), Atlantogenata and Metatheria.