Studies on the molecular evolution of MHC class I genes and their polymorphism

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The molecules that belong to the MHC family possess unique domains that correspond to the peptide-binding domains of the MHC class I and class II molecules. The origin of these domains and the diversification of the two classes has not been clarified yet. To understand the molecular evolution of the MHC family and to understand the mechanism of the production of high polymorphism of the classical MHC class I genes, we have investigated various divergent MHC-related genes from various animals. In the present study, we investigated the highly divergent MHC-related genes from the most primitive jawed vertebrates, namely, the cartilaginous fish, and revealed a unique gene cluster in these interesting animals. We also investigated the divergent MHC-related molecule, MR1, at the protein level, and revealed that the MR1 heavy chain associates with beta2-microglobulin. We speculated that the MR1 molecule may possess a structure highly similar to that of the classical MHC class I molecule. The unique characteristics of MR1 molecule may be important to understand the molecular evolution of the MHC family members. We further investigated the classical MHC class I genes from rainbow trout, and revealed that the classical MHC class I genes composed of highly divergent sequence lineages share a single locus in this fish. The results indicated that the additional high polymorphism observed in rainbow trout was produced by the various combination of different lineages of alphal1 and alpha2 domains.