The origin and evolution of major histocompatibility complex (MHC).

主要组织相容性复合体(MHC)包含一个基因家族，其产物在自我和非自我区分中起着至关重要的作用。自体是一个人自己的多肽，它与MHC分子结合，限制胸腺中的T细胞库，而非自体是外源抗原的加工多肽，可以在MHC分子的背景下存在，并触发免疫反应。由于MHC分子控制的免疫系统影响个体的生存，MHC本身的双重功能必须受到自然选择的影响。这一国际科学研究计划的重点是(1)DNA序列分析和种群遗传学理论关于MHC分子的起源和进化；(2)从MHC多样性的角度探讨人类的起源。(1)MHC分子的起源和进化：虽然人们曾多次尝试从无颌鱼和低等脊椎动物中分离MHC基因，但均未成功。这表明MHC是在…进化的脊椎动物更早期的进化阶段。由于脊椎动物的免疫系统涉及免疫球蛋白和T细胞受体基因，基因组重排的分子机制也是在MHC出现的同时获得的。我们争论过，为什么免疫系统和脊椎动物的进化在身体的复杂性和后代的数量方面是平行出现的。MHC基因的自然选择与MHC分子的双重功能密切相关，而选择是物种内MHC分子异常多样性的原因。我们已经估计了对MHC分子进行自然选择的强度，并基于这个估计，我们计划制定一个濒危物种保护计划。自然选择的动因是寄生虫：这些和MHC变种一直在共同进化。不同地理区域的不同寄生虫是人类MHC(人类白细胞抗原)分化的部分原因。最近社会的变化和环境的改善意味着对MHC的自然选择的放松或多样性的丧失，从而对未来人类的防御系统提出了一个严重的问题。(2)人类MHC的多样性和局部分化。人类白细胞抗原的局部分化反映了不同寄生虫的局部选择以及过去不同的迁移途径。相反，目前的人类白细胞抗原分布允许我们推断我们祖先的迁徙路线。我们提出了一种特别参考重组分数来寻找消失的迁移路径的方法。这种方法使我们能够估计种群迁移发生的时间和之间：重组比例越高，迁移事件越新。最后，我们研究了植物自交不亲和性的起源，因为它的理论基础与MHC相似。我们已经指出，自交亲和系统的出现与开花植物的出现是一致的，并将进一步调查原因。较少

The major histocompatibility complex (Mhc) contains a family of genes whose products play crucial roles in self and nonself discrimination. Self is one's own peptides that bind to Mhc molecules and restrict the T-cell repertoire in the thymus, whereas nonself is processed peptides of foreign antigens that can be presented in the context of Mhc molecules and trigger the immune response. Since the immune system thus controlled by Mhc molecules affects the survival of individuals, the dual function of Mhc itself must be subjected to natural selection. This international scientific research program has focused on (1) DNA sequence analysis and population genetics theory on the origin and evolution of Mhc molecules and (2) the origin of mankind from a viewpoint of the Mhc diversity.(1) The origin and evolution of Mhc molecules : Although a number of attempts were made to isolate Mhc genes from jawless fishes and lower vertebrates, all were unsuccessful. This indicates that Mhc evolved at the … More early evolutionary stage of vertebrates. Since the vertebrate immune system involves Ig and T cell receptor genes, the molecular mechanism of genomic rearrangement was also acquired around the same time as the emergence of Mhc. We have argued why the immune system and the vertebrate evolution emerged in parallel in terms of the complexity of body and the number of offspring. Natural selection for Mhc genes is intimately related to the dual function of Mhc Molecules and selection is responsible for an extraordinary diversity of Mhc molecules within a species. We have estimated the intensity of natural selection operating on Mhc molecules, and based on this estimate, we plan to develop a conservation program for endangered species. The agent of natural selection is parasites : These and Mhc variants have been coevolving. Different parasites in different geographic regions are in part a cause of human Mhc (HLA) differentiation. Recent change in our society and improvement of environment suggest relaxation of natural selection for Mhc or loss of the diversity, thus posing a serious question on the defense system in the future mankind.(2) Diversity and local differentiation of human Mhc (HLA). Local differentiation of HLA is a reflection of local selection owing to different parasites as well as migration routes in the past. Conversely, the current HLA distribution allows us to infer migration routes of our ancestors. We have proposed a method in searching for vanished migration routes with special reference to recombination fraction. This method allows us to estimate when and among which populations migrations occurred : The higher the recombination fraction, the more recent migration event.Finally we have studied the origin of self-incompatibility in plants because the theoretical basis is similar to that for Mhc. We have pointed out that the emergence of selfincompatibility system coincided with the emergence of flowering plants, and will further investigate why. Less