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发现表达 KIR 的 C1 配体的大猩猩 MHC-C。

Discovery of gorilla MHC-C expressing C1 ligand for KIR.

机构信息

Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103, Leipzig, Germany.

出版信息

Immunogenetics. 2018 May;70(5):293-304. doi: 10.1007/s00251-017-1038-y. Epub 2017 Nov 3.

DOI:10.1007/s00251-017-1038-y
PMID:29101448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5899755/
Abstract

In comparison to humans and chimpanzees, gorillas show low diversity at MHC class I genes (Gogo), as reflected by an overall reduced level of allelic variation as well as the absence of a functionally important sequence motif that interacts with killer cell immunoglobulin-like receptors (KIR). Here, we use recently generated large-scale genomic sequence data for a reassessment of allelic diversity at Gogo-C, the gorilla orthologue of HLA-C. Through the combination of long-range amplifications and long-read sequencing technology, we obtained, among the 35 gorillas reanalyzed, three novel full-length genomic sequences including a coding region sequence that has not been previously described. The newly identified Gogo-C03:01 allele has a divergent recombinant structure that sets it apart from other Gogo-C alleles. Domain-by-domain phylogenetic analysis shows that Gogo-C03:01 has segments in common with Gogo-B07, the additional B-like gene that is present on some gorilla MHC haplotypes. Identified in ~ 50% of the gorillas analyzed, the Gogo-C03:01 allele exclusively encodes the C1 epitope among Gogo-C allotypes, indicating its important function in controlling natural killer cell (NK cell) responses via KIR. We further explored the hypothesis whether gorillas experienced a selective sweep which may have resulted in a general reduction of the gorilla MHC class I repertoire. Our results provide little support for a selective sweep but rather suggest that the overall low Gogo class I diversity can be best explained by drastic demographic changes gorillas experienced in the ancient and recent past.

摘要

与人类和黑猩猩相比,大猩猩在 MHC Ⅰ类基因(Gogo)上显示出较低的多样性,这反映在等位基因变异水平总体降低,以及缺乏与杀伤细胞免疫球蛋白样受体(KIR)相互作用的功能重要序列基序。在这里,我们使用最近生成的大规模基因组序列数据,重新评估了 HLA-C 大猩猩同源物 Gogo-C 的等位基因多样性。通过长距离扩增和长读测序技术的结合,在重新分析的 35 只大猩猩中,我们获得了三个新的全长基因组序列,其中包括一个以前未描述的编码区序列。新鉴定的 Gogo-C03:01 等位基因具有独特的重组结构,与其他 Gogo-C 等位基因不同。基于结构域的系统发育分析表明,Gogo-C03:01 与 Gogo-B07 具有共同的片段,Gogo-B07 是一些大猩猩 MHC 单体型上存在的额外的 B 样基因。在分析的大约 50%的大猩猩中发现,Gogo-C*03:01 等位基因仅在 Gogo-C 同种异型中编码 C1 表位,表明其在通过 KIR 控制自然杀伤细胞(NK 细胞)反应方面具有重要功能。我们进一步探讨了大猩猩是否经历了选择清除的假说,这可能导致大猩猩 MHC Ⅰ类 repertoire 的普遍减少。我们的结果几乎不支持选择清除,而是表明大猩猩 MHC Ⅰ类多样性总体较低,这可以最好地解释为大猩猩在古代和近代经历的剧烈人口变化。

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本文引用的文献

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Immunogenetics. 2017 May;69(5):303-323. doi: 10.1007/s00251-017-0974-x. Epub 2017 Mar 22.
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