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

MHC I类基因的分子进化及其多态性研究

基本信息

批准号：
13670324
负责人：
HASHIMOTO Keiichiro
金额：
$ 2.3万
依托单位：
Fujita Health University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670324/
关键词：
MHC Class I polymorphism molecular evolution acquired immunity cartilaginous fish

项目摘要

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.

属于MHC家族的分子具有与MHC I类和II类分子的多肽结合结构域相对应的独特结构域。这些领域的起源以及这两个类别的多样性尚未得到澄清。为了了解MHC家族的分子进化和经典MHC I类基因高度多态的产生机制，我们研究了不同动物中各种差异的MHC相关基因。在本研究中，我们研究了最原始的有颌骨脊椎动物，即软骨鱼的高度差异的MHC相关基因，并揭示了这些有趣的动物中一个独特的基因簇。我们还在蛋白质水平上研究了分化的MHC相关分子MR1，发现MR1重链与β2-微球蛋白有关。我们推测，MR1分子可能具有与经典MHC I类分子高度相似的结构。MR1分子的独特特性可能对了解MHC家族成员的分子进化具有重要意义。我们进一步研究了虹鳟鱼的经典MHC I类基因，发现由高度分化的序列谱系组成的经典MHC I类基因在这种鱼中共享一个单一的基因座。结果表明，虹鱼体内观察到的额外的高多态性是由不同的alphal1和alpha2结构域的不同谱系的不同组合产生的。