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

我们报道了从鲨鱼(Triakis Scyllia)中分离出高度多态的MHC I类基因并进行了广泛的分析，这些基因属于最原始的有颌骨的脊椎动物类群-软骨鱼。预测的完整多肽结合区保留了与抗原肽末端相互作用的关键氨基酸残基，并显示了广泛的等位基因多态性，可与人类经典的MHC I类分子的等位基因多态性相媲美。在这些区域中有明显的镶嵌结构，这表明重组机制可以创造等位基因多样性。本研究证明了在脊椎动物进化的原始阶段，MHC-I类分子所采用的基本抗原提呈策略的建立和两个多态MHC类分子的完全分化。高度多态的鲨鱼MHC-I类基因完整的多肽结合域的阐明为我们提供了一个机会，根据对MHC-I类分子结构研究的最新进展，我们有机会检验其预测的蛋白质产物的特征。这些结果表明，MHC-I类分子/肽复合体的T细胞识别的基本特征有望在脊椎动物进化的早期阶段建立。阐明鱼类中典型的经典I类分子以及一些与MHC I类分子相关的分子有助于我们探索古代I类分子的共同点。

We report the isolation and extensive analyses of highly polymorphic MHC class I genes from sharks (Triakis scyllia), that belong to the most primitive vertebrate group with jaws, the cartilaginous fish. Predicted complete peptide-binding domains showed retention of the critical amino acid residues that would interact with antigenic peptide termini and revealed extensive allelic polymorphism that can be comparable to those of human classical MHC class I molecules. Mosaic structures are apparent in these domains suggesting recombinational mechanisms to create allelic diversity. The present study demonstrated establishment of the basic strategy for antigen-presentation employed by MHC class I molecules and complete divergence of two polymorphic MHC classes at a phylogenetically primitive stage of vertebrate evolution.The elucidation of the complete peptide-binding domains of the highly polymorphic shark MHC class I genes offered us an opportunity to examine the characteristics of their predicted protein products in the light of the latest advance in the structural studies on the MHC class I molecules. The results suggest that the fundamental characteristics in the T cell recognition of the MHC class I molecule/peptide complex are expected to have been established at the early stage of the vertebrate evolution. The elucidation of the typical classical class I molecules from fishes and also of some MHC class I-related molecules may help us to explore the common denominator of the ancient class I molecules.