EVOLUTION OF NOVEL NON CLASSICAL MHC CLASS I GENE IN OLD WORLD PRIMATES

旧世界灵长类动物新型非经典 MHC I 类基因的进化

• 批准号: 6312933
• 负责人: David I Watkins
• 金额: $ 7.08万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-06-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6312933
• 关键词: Mammalia; animal tissue; immunology; inborn metabolism disorder; inflammation; technology /technique; transplantation

OBJECTIVE To evaluate the conservation of the MHC-E locus throughout anthropoid primate evolution, we identified the homologue of the HLA-E locus in six different New World monkey species. RESULTS Full-length sequencing of MHC-E cDNAs in four unrelated cotton-top tamarins (Saguinus oedipus) revealed no evidence for polymorphism. Using the PCR, denaturing gradient gel electrophoresis, and direct sequencing, we also identified MHC-E alleles in five other New World monkey species, representing all extant platyrrhine families. In contrast to all other classical and nonclassical MHC class I genes in primates, the rate of synonymous nucleotide substitution is much greater than the rate of nonsynonymous nucleotide substitution within exons 2 and 3 encoding the peptide binding region (PBR) in MHC-E genes. DISCUSSION The PBR of the MHC-E molecule has evolved under purifying selective pressures, and the very unusual evolutionary history of this ancient gene provides further evidence that the products of the HLA-E locus serve a critical immunological function. FUTURE DIRECTIONS Given the remarkable conservation of the PBR during primate evolution, this critical immunological function is probably related to the peptide binding ability of the MHC-E protein. KEY WORDS MHC, HLA-E, New World FUNDING NIH RR00167, DK44886 PUBLICATIONS Knapp, LA, Cadavid, LF, and D.I. Watkins. 1998. The MHC-E locus is the most ancient and well-conserved of all known primate class I histocompatibility genes. J. Immunol. 160:189-196.

目的评价MHC-E基因座的保守性 在灵长类动物的进化过程中，我们发现了 HLA-E基因座的基因组序列。 结果 四株无关棉尖叶病MHC-E基因的全长序列分析 罗望子（Saguinus oedipus）没有发现多态性的证据。 采用PCR、变性梯度凝胶电泳和直接 通过测序，我们还在其他五个新世界中鉴定了MHC-E等位基因， 猴子物种，代表所有现存的阔鼻科。 在 与所有其他经典和非经典MHC I类基因相比， 在灵长类动物中，同义核苷酸替换的速率非常高， 大于非同义核苷酸取代的速率， 编码MHC-E中肽结合区（PBR）的外显子2和3 基因. 讨论MHC-E分子的PBR已经在 净化选择压力，和非常不寻常的进化 这个古老基因的历史提供了进一步的证据， HLA-E基因座的产物具有关键的免疫功能。 未来的方向鉴于PBR在2010年期间的显著保护， 灵长类动物的进化，这种关键的免疫功能可能是 与MHC-E蛋白的肽结合能力有关。 关键 词语MHC，HLA-E，新世界基金NIH RR 00167，DK 44886出版物 克纳普，洛杉矶，卡达维德，LF和D.I. Watkins 1998. MHC-E基因座是 是所有已知灵长类动物中最古老和保存最完好的一类 组织相容性基因 160：189-196。