Evolution of major histocompatibility complex genes in mammals

Major Histocompatibility Complex class I (Mhc-I) molecules play an essential role in adaptive immune responses of all jawed vertebrates. Most studies characterizing mammalian Mhc-I genes have been carried out in members of a single mammalian subclass, the Eutheria, or placental mammals. In this study, research concerning evolution and structure of Mhc-I has been extended to members of the two other mammalian subclasses: marsupials and monotremes. This study focuses on two major aspects of Mhc-I (1) description of the number of Mhc-I loci in a single marsupial, Monodelphis domestica, and (2) characterization of monotreme Mhc-I genes. This study provides the first opportunity to study the evolution of Mhc-I genes in all three mammalian lineages.; Using a combination of cDNA and genomic analysis, sequences from three Mhc-I loci were identified in M. domestica. Two of the loci represent a recent Mhc-I gene duplication which occurred 2.9 to 3.7 million years ago. Efforts to characterize Mhc-I genes from the short-beaked echidna and the duck-billed platypus resulted in the first isolation of functional as well as non-functional, Mhc-I sequences from any monotreme. From phylogenetic analysis of Mhc-I sequences it is clear that mammalian Mhc-I genes are derived from three different ancestral Mhc-I genes. This pattern of evolution would require two rounds of duplications and deletions at the mammalian Mhc-I to account for the current Mhc-I genes present in each mammalian subclass. This research expands the knowledge of monotreme and marsupial Mhc-I, allows the analysis of Mhc-I evolution in all mammalian subclasses, and has significance for mammalian systematics.