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关键作用。自体是与Mhc分子结合并限制胸腺中t细胞库的自身肽，而非自体是外源抗原的加工肽，可以在Mhc分子的背景下呈现并触发免疫反应。由于由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服从自然选择。这一国际科研项目主要集中在(1)从Mhc分子的起源和进化的DNA序列分析和群体遗传学理论；(2)从Mhc多样性的角度研究人类的起源。(1) Mhc分子的起源和进化：尽管人们曾多次尝试从无颌鱼类和低等脊椎动物中分离Mhc基因，但都没有成功。这表明Mhc是在脊椎动物更早期的进化阶段进化的。由于脊椎动物免疫系统涉及Ig和T细胞受体基因，基因组重排的分子机制也在Mhc出现的同时获得。我们讨论了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上是并行出现的。Mhc基因的自然选择与Mhc分子的双重功能密切相关，并且选择负责物种内Mhc分子的非凡多样性。我们估计了Mhc分子的自然选择强度，并在此基础上，我们计划制定濒危物种保护计划。自然选择的媒介是寄生虫：这些和Mhc变体一直在共同进化。不同地理区域的不同寄生虫是人类Mhc （HLA）分化的部分原因。近年来社会的变化和环境的改善暗示着Mhc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严重的问题。(2)人Mhc （HLA）的多样性和局部分化。HLA的局部分化是过去由于寄生虫和迁移途径的不同而产生的局部选择的反映。相反，目前的HLA分布允许我们推断我们祖先的迁移路线。提出了一种基于重组分数的迁移路径消失搜索方法。这种方法使我们能够估计种群迁移发生的时间和范围：重组分数越高，迁移事件越近。最后，我们研究了植物自交不亲和的起源，因为其理论基础与Mhc相似。我们已经指出自交不亲和系统的出现与开花植物的出现是同时发生的，并将进一步探讨其原因。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