Origin and evolution of MHC class I and MIC genes in primates

灵长类 MHC I 类和 MIC 基因的起源和进化

• 批准号: 13640717
• 负责人: TATENO Yoshio
• 金额: $ 2.18万
• 依托单位: National Institute of Genetics
• 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-13640717/
• 关键词: MHC class genomic region; molecular evolution; genome analysis; genome fragment duplication; LINE; neutral evolution; divergence time; primate evolution; HLAクラスI遺伝子領域

MHC system is considered to be originated in protochordata more than 300 million years ago, and has since been modified and refined in evolution up to the present system in vertebrates. In this process various evolutionary factors have been involved not only in MHC genic regions but also in other genomic regions. Therefore, it is desirable that evolutionary analysis be carried out in both the genic and non-genic regions in MHC genome sequences. We have made evolutionary analyses of a MHC Class I genomic region for man (M), chimpanzee (C) and Rhesus monkey (R) focusing particularly on the evolutionary origin of B and C genes and that of MICA and MICB genes. It is known that each pair is located respectively in a pair genome fragments that were originated by genome fragment duplication. To estimate the evolutionary origin of each pair of the genes, therefore, we were to estimate the duplication time of each pair of the genome fragments. It is noted that sine the MHC genes have been subject to strong positive selection in evolution, the genes have not evolved constantly over time making them unsuitable for the estimation. We thus paid attention to orthologous LINE fragments between the pair of the genome fragments that have coevolved with the MHC genes, but constantly over time because they have lost their functions before the duplication of the genome fragments. For calibration we adopted an estimate of the divergence time between man and chimpanzee as 5.4 million years (MY) ago. We then estimated the origin of MHC B and MHC C genes as far back as 22.3 MY ago, and that of MICA and MICE as far back as 14.1 MY ago. The validity of these estimates were confirmed by our new achievement that the divergence time of Rhesus monkey has been estimated as 27.0 MY ago.

MHC系统被认为起源于3亿多年前的原索动物，并在进化过程中不断修改和完善，直到脊椎动物中的现有系统。在这一过程中，各种进化因素不仅涉及MHC基因区，而且涉及其他基因组区域。因此，希望在MHC基因组序列的基因区和非基因区进行进化分析。我们对人（M）、黑猩猩（C）和恒河猴（R）的MHC I类基因组区域进行了进化分析，特别关注B和C基因以及云母和MIC B基因的进化起源。已知每对分别位于由基因组片段复制产生的一对基因组片段中。因此，为了估计每对基因的进化起源，我们要估计每对基因组片段的复制时间。值得注意的是，由于MHC基因在进化过程中受到了强烈的正选择，因此这些基因并没有随着时间的推移不断进化，这使得它们不适合用于估计。因此，我们注意到了与MHC基因共同进化的基因组片段对之间的正向同源序列片段，但随着时间的推移，它们不断地进化，因为它们在基因组片段复制之前已经失去了功能。为了进行校准，我们采用了人类和黑猩猩之间的分歧时间估计为540万年前。然后，我们估计MHC B和MHC C基因的起源可以追溯到22.3万年前，云母和MICE的起源可以追溯到14.1万年前。这些估计的有效性得到了我们的新成果的证实，恒河猴的分歧时间已被估计为27.0 MY前。

项目成果

Shiina T, Ando A, Suto Y, Kasai , Shigenari A, Takishima N, Kikkawa E, Iwata K, Kuwano Y, Kitamura Y, Matsuzawa Y, Sano K, Nogami M, Kawata H , Li S, Fukuzumi Y, Yamazaki M, Tashiro H, Tamiya G , Kohda A, Okumura K, Ikemura T, Soeda E, Mizuki N, Kimura M,

Shiina T、Ando A、Suto Y、Kasai、Shigenari A、Takishima N、Kikkawa E、Iwata K、Kuwano Y、Kitamura Y、Matsuzawa Y、Sano K、Nogami M、Kawata H、Li S、Fukuzumi Y、Yamazaki M、

Abi-Rached L, Gilles A, Shiina T, Pontarotti P, Inoko H: "Evidence of en bloc duplication in vertebrate genomes"Nature Genetics. 31. 100-105 (2002)

Abi-Rached L、Gilles A、Shiina T、Pontarotti P、Inoko H：“脊椎动物基因组中整体复制的证据”《自然遗传学》。

Kulski JK, Dunn DS, Gaudieri S, Shiina T, Inoko H: "Genomic and phylogenic analysis of the human CD1 and HLA class I multicopy genes"J Mol Evol.. 53. 642-650 (2001)

Kulski JK、Dunn DS、Gaudieri S、Shiina T、Inoko H：“人类 CD1 和 HLA I 类多拷贝基因的基因组和系统发育分析”J Mol Evol.. 53. 642-650 (2001)

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《国际人类基因组测序联盟：人类基因组的初步测序和分析》《自然》。

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