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

属于MHC家族的分子具有对应于MHC I类和II类分子的肽结合结构域的独特结构域。这些领域的起源和这两个类别的多样化尚未澄清。为了了解MHC家族的分子进化和理解经典MHC I类基因的高多态性的产生机制，我们研究了来自各种动物的各种不同的MHC相关基因。在本研究中，我们调查了最原始的有颌脊椎动物，即软骨鱼的高度分歧的MHC相关基因，并揭示了这些有趣的动物中的一个独特的基因簇。我们还研究了不同的MHC相关分子，MR 1，在蛋白质水平上，并揭示了MR 1重链与β 2-微球蛋白。我们推测MR 1分子可能具有与经典的MHC I类分子高度相似的结构。MR 1分子的独特特性对理解MHC家族成员的分子进化可能具有重要意义。我们进一步研究了虹鳟鱼的经典MHC I类基因，并揭示了由高度不同的序列谱系组成的经典MHC I类基因在虹鳟鱼中共享一个位点。结果表明，在虹鳟鱼中观察到的额外的高多态性是由不同谱系的α 1和α 2结构域的各种组合产生的。

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.