Data from: A comprehensive analysis of teleost MHC class I sequences

Background: MHC class I (MHCI) molecules are the key presenters of peptides generated through the intracellular pathway to CD8-positive T-cells. In fish, MHCI genes were first identified in the early 1990′s, but we still know little about their functional relevance. The expansion and presumed sub-functionalization of cod MHCI and access to many published fish genome sequences provide us with the incentive to undertake a comprehensive study of deduced teleost fish MHCI molecules. Results: We expand the known MHCI lineages in teleosts to five with identification of a new lineage defined as P. The two lineages U and Z, which both include presumed peptide binding classical/typical molecules besides more derived molecules, are present in all teleosts analyzed. The U lineage displays two modes of evolution, most pronouncedly observed in classical-type alpha 1 domains; cod and stickleback have expanded on one of at least eight ancient alpha 1 domain lineages as opposed to many other teleosts that preserved a number of these ancient lineages. The Z lineage comes in a typical format present in all analyzed ray-finned fish species as well as lungfish. The typical Z format displays an unprecedented conservation of almost all 37 residues predicted to make up the peptide binding groove. However, also co-existing atypical Z sub-lineage molecules, which lost the presumed peptide binding motif, are found in some fish like carps and cavefish. The remaining three lineages, L, S and P, are not predicted to bind peptides and are lost in some species. Conclusions: Much like tetrapods, teleosts have polymorphic classical peptide binding MHCI molecules, a number of classical-similar non-classical MHCI molecules, and some members of more diverged MHCI lineages. Different from tetrapods, however, is that in some teleosts the classical MHCI polymorphism incorporates multiple ancient MHCI domain lineages. Also different from tetrapods is that teleosts have typical Z molecules, in which the residues that presumably form the peptide binding groove have been almost completely conserved for over 400 million years. The reasons for the uniquely teleost evolution modes of peptide binding MHCI molecules remain an enigma.

背景：主要组织相容性复合体I类（MHC class I，MHCI）分子是细胞内通路产生的肽段向CD8阳性T细胞呈递的关键载体。鱼类的MHCI基因最早于20世纪90年代初被鉴定，但目前对其功能相关性仍知之甚少。鳕鱼MHCI的扩增及推定亚功能化，加上大量已发表的鱼类基因组序列资源，为我们全面研究推定的硬骨鱼MHCI分子提供了研究契机。
结果：本研究通过鉴定命名为P的新谱系，将硬骨鱼已知的MHCI谱系扩展至5个。所分析的所有硬骨鱼中均存在U和Z两个谱系，二者均包含推定的肽结合经典/典型分子及更为分化的分子。U谱系展现出两种进化模式，这一特征在经典型α1结构域中最为显著：鳕鱼和棘鱼在至少8个古老α1结构域谱系中的一个上发生了扩增，而其他多数硬骨鱼则保留了多个这类古老谱系。Z谱系存在于所有分析过的辐鳍鱼类以及肺鱼中，其典型形式的肽结合沟槽相关的37个残基几乎完全保守，这一现象此前未见报道。此外，在鲤鱼、洞穴鱼等部分鱼类中还存在非典型的Z亚谱系分子，这类分子丢失了推定的肽结合基序。其余三个谱系L、S和P均不具备肽结合能力，且在部分物种中发生了丢失。
结论：与四足动物类似，硬骨鱼拥有多态性的经典肽结合MHCI分子、多个类经典的非经典MHCI分子，以及一些分化程度更高的MHCI谱系成员。但与四足动物不同的是，部分硬骨鱼的经典MHCI多态性整合了多个古老的MHCI结构域谱系。此外，硬骨鱼还拥有典型的Z分子，其推定构成肽结合沟槽的残基在超过4亿年的进化中几乎完全保守，这一点也与四足动物不同。硬骨鱼肽结合MHCI分子的独特进化模式的成因仍为未解之谜。