Origins and divergence times of mammalian class II MHC gene clusters

Abstract

The class I and II major histocompatibility complex (MHC) genes are apparently subject to evolution by a birth-and-death process. The rate of gene turnover is much slower in the latter genes than in the former. In placental mammals, the class II region can be subdivided into different orthologous subregions or gene clusters (DR, DQ, DO, and DN), but the origins and evolutionary relationships of these gene clusters are not well established. Here we 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 α-chain and β-chain gene clusters are shared by placental mammals and marsupials, but the gene clusters from non- mammalian species are paralogous to mammalian gene clusters. We estimated the times of divergence between gene clusters in placental mammals using the linearized tree and distance regression methods. Our results indicate that most gene clusters originated 170-200 million years (MY) ago, but that DO β- chain genes diverged from the other β-chain gene clusters approximately 210- 260 MY ago. The phylogenetic trees for the α- and β-chain genes were not congruent, suggesting that the evolutionary history of the class II gene clusters is more complex than previously thought.