Origins and divergence times of mammalian class II MHC gene clusters

The class I and II major histocompatibility complex (MHC) genes are apparen tly subject to evolution by a birth-and-death process. The rate of gene tur nover is much slower in the latter genes than in the former. In placental m ammals, the class II region can be subdivided into different orthologous su bregions or gene clusters (DR, DQ, DO, and DN), but the origins and evoluti onary relationships of these gene clusters are not well established. Here w e report: the results of our study of the times of origin and evolutionary relationships of these gene clusters in mammals. Our analysis suggests that both class II alpha-chain and beta-chain gene clusters are shared by place ntal mammals and marsupials, but the gene clusters from nonmammalian specie s are paralogous to mammalian gene dusters. We estimated the times of diver gence between gene clusters in placental mammals using the linearized tree and distance regression methods. Our results indicate that most gene cluste rs originated 170-200 million years (MY) ago, but that DO beta-chain genes diverged from the other beta-chain gene clusters approximately 210-260 MY a go. The phylogenetic trees for the alpha- and beta-chain genes were not con gruent, suggesting that the evolutionary history of the class II gene clust ers is more complex than previously thought.