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在新世界猴的 T 细胞受体β基因的互补决定区中,正选择压力增加。

Increased positive selection pressure within the complementarity determining regions of the T-cell receptor β gene in New World monkeys.

机构信息

Laboratory of Immune Regulation, Wakayama Medical University, Osaka, Japan.

出版信息

Am J Primatol. 2011 Oct;73(10):1082-92. doi: 10.1002/ajp.20976. Epub 2011 Jul 18.

Abstract

Because of the long-term co-evolution of TCR and MHC molecules, numerous nucleotide substitutions have accumulated within the domains of TCRβ genes. We previously found that nonsynonymous nucleotide substitutions occurred more frequently in complementarity determining region (CDR)β than in CDRα, even though only a limited number of common marmoset (Callithrix jacchus) and human T-cell receptor β variable (TRBV) sequences were compared. This interesting finding raised the question of whether the increased selective pressure within CDRβ was species-specific. In this study, we identified 21 TRBV region sequences from the common marmoset and performed comparative sequence analyses of the T-cell receptor α variable (TRAV) and TRBV regions from human, chimpanzee, rhesus monkey, cotton-top tamarin, Ma's night monkey, and common marmoset. The ratios of the number of nonsynonymous nucleotide substitutions per site (d(N) ) to the d(S) values (d(N) /d(S) ) were less than 1 within the framework regions (FRs) of TRAV and TRBV region sequences, suggesting that purifying selection is largely dominant within the FRs. In contrast, the d(N) values were statistically significantly greater for CDRβ than for CDRα only in New World monkeys. Also, increased d(N) /d(S) ratios (d(N) /d(S) >1) were observed within CDRβ between humans and New World monkeys and, interestingly, between New World monkeys, which share a relatively recent common ancestor. Moreover, phylogenetic analysis by maximum likelihood analysis provided firm evidence to support that positive selection occurred within CDRβ along New World monkey lineages. These results suggest that increased positive selection pressure within CDRβ is common in New World monkeys rather than being species-specific. This study provides an intriguing insight into the co-evolution of TCR and MHC molecules within primates.

摘要

由于 TCR 和 MHC 分子的长期共同进化,TCRβ 基因的结构域中积累了大量核苷酸取代。我们之前发现,尽管仅比较了有限数量的普通狨猴(Callithrix jacchus)和人类 T 细胞受体β可变(TRBV)序列,但互补决定区(CDR)β中的非同义核苷酸取代比 CDRα 更频繁发生。这个有趣的发现提出了一个问题,即在 CDRβ 中增加的选择压力是否具有物种特异性。在这项研究中,我们从普通狨猴中鉴定了 21 个 TRBV 区序列,并对人类、黑猩猩、恒河猴、棉顶狨猴、Ma 的夜猴和普通狨猴的 T 细胞受体α可变(TRAV)和 TRBV 区进行了比较序列分析。TRA 和 TRBV 区序列框架区(FR)内每个位置非同义核苷酸取代数(d(N))与同义核苷酸取代数(d(S))的比值(d(N)/d(S))均小于 1,表明 FR 内主要存在纯化选择。相比之下,仅在新世界猴中,CDRβ 的 d(N)值明显大于 CDRα。此外,在人类和新世界猴之间以及有趣的是在新世界猴之间,CDRβ 内的 d(N)/d(S)比值(d(N)/d(S)>1)增加,这些猴类共享一个相对较近的共同祖先。此外,最大似然分析的系统发育分析提供了确凿的证据,支持在新世界猴谱系中 CDRβ 内发生了正选择。这些结果表明,在新世界猴中,CDRβ 内增加的正选择压力是普遍存在的,而不是具有物种特异性。这项研究为灵长类动物中 TCR 和 MHC 分子的共同进化提供了一个有趣的视角。

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