PLoS Pathogens:研究揭示HIV靶向蛋白的进化历史
美国科学家近日研究发现，一种名为TRIMCyp的能够标靶HIV等多种病毒的蛋白，在灵长动物（人类除外）中进行了两次进化，其中一个版本的进化时间在1000万年前和500万年前之间。该结果表明，这些病毒在灵长动物的进化中起到了重要的作用。相关论文发表在《公共科学图书馆·病原体》（PLoS Pathogens）上。
之前有研究发现，新世界猫头鹰猴（New World owl monkeys）具有TRIMCyp蛋白，它能够抵御HIV-1和其它种类的慢病毒（lentivirus）。近日有多个研究小组报告在多个旧世界猴（Old World monkeys）种属体内发现了一种类似的蛋白。由于这两种蛋白之间存在充分的差别，因而研究人员认为它们是分别独立进化的。
在旧世界猴中，发现TRIMCyp的有猪尾猕猴（Macaca nemestrina）、长尾猕猴（M. fascicularis）及恒河猴（rhesus macaques）等。这些猴子于大约500万年前由共同祖先分化而来，所以有科学家推测，这种蛋白至少应有500万年的历史。
在最新的研究中，由美国哈佛医学院的Welkin Johnson领导的研究小组报告说，TRIMCyp蛋白在另一种相关的旧世界猴——乌黑白眉猴体内并不存在，而乌黑白眉猴是于大约1000万年前从猕猴世系中分化而来。Johnson认为：“这意味着1000万年前至500万年前之间，在灵长动物中流行着慢病毒。”
美国西雅图佛瑞德·哈金森癌症研究中心的Michael Emerman表示，关于灵长类慢病毒家族的年龄争论已久，一些人认为它只有几千年的历史。新的发现支持了这样一种假说，即这些病毒已经“折磨”了灵长动物数百万年。
美国加州大学洛杉矶分校的传染病学家Nathan Wolfe认为，TRIMCyp的趋同进化（convergent evolution）证明了灵长类进化过程中逆转录酶病毒防御的重要性。他说：“当你注意到了趋同进化，一般来说它就是相当强大的自然选择力的标记。这一研究强调了逆转录酶病毒对于非人类灵长类的进化是多么重要。”（科学网 梅进/编译）
生物谷推荐原始出处：
（PLoS Pathogens），doi:10.1371/journal.ppat.1000003，Ruchi M. Newman，Welkin Johnson
Evolution of a TRIM5-CypA Splice Isoform in Old World Monkeys
Ruchi M. Newman, Laura Hall, Andrea Kirmaier, Lu-Ann Pozzi, Erez Pery, Michael Farzan, Shawn P. O'Neil, Welkin Johnson
Abstract
The TRIM family proteins share a conserved arrangement of three adjacent domains, an N-terminal RING domain, followed by one or two B-boxes and a coiled-coil, which constitutes the tripartite-motif for which the family is named. However, the C-termini of TRIM proteins vary, and include at least nine evolutionarily distinct, unrelated protein domains. Antiviral restriction factor TRIM5α has a C-terminal B30.2/SPRY domain, which is the major determinant of viral target specificity. Here, we describe the evolution of a cyclophilin-A encoding exon downstream of the TRIM5 locus of Asian macaques. Alternative splicing gives rise to chimeric transcripts encoding the TRIM motif fused to a C-terminal CypA domain (TRIM5-CypA). We detected TRIM5-CypA chimeric transcripts in primary lymphocytes from two macaque species. These were derived in part from a CypA pseudogene in the TRIM5 locus, which is distinct from the previously described CypA insertion in TRIM5 of owl monkeys. The CypA insertion is linked to a mutation in the 3′ splice site upstream of exon 7, which may prevent or reduce expression of the α-isoform. All pig-tailed macaques (M. nemestrina) screened were homozygous for the CypA insertion. In contrast, the CypA-containing allele was present in 17% (17/101) of rhesus macaques (M. mulatta). The block to HIV-1 infection in lymphocytes from animals bearing the TRIM5-CypA allele was weaker than that in cells from wild type animals. HIV-1 infectivity remained significantly lower than SIV infectivity, but was not rescued by treatment with cyclosporine A. Thus, unlike owl monkey TRIMCyp, expression of the macaque TRIM5-CypA isoform does not result in increased restriction of HIV-1. Despite its distinct evolutionary origin, Macaca TRIM5-CypA has a similar domain arrangement and shares ~80% amino-acid identity with the TRIMCyp protein of owl monkeys. The independent appearance of TRIM5-CypA chimeras in two primate lineages constitutes a remarkable example of convergent evolution. Based on the presence of the CypA insertion in separate macaque lineages, and its absence from sooty mangabeys, we estimate that the Macaca TRIM5-CypA variant appeared 5–10 million years ago in a common ancestor of the Asian macaques. Whether the formation of novel genes through alternative splicing has played a wider role in the evolution of the TRIM family remains to be investigated.
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