Identification of a genomic reservoir for new TRIM genes in primate genomes.
Identification of a genomic reservoir for new TRIM genes in primate genomes.
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DOI：
10.1371/journal.pgen.1002388
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发表时间：
2011-12
期刊：
影响因子：
4.5
通讯作者：
Sawyer SL
中科院分区：
文献类型：
--
作者：
Han K;Lou DI;Sawyer SL
Tripartite Motif （TRIM）泛素连接酶在对抗病毒的先天免疫应答中起作用。TRIM5α是该家族中最具特征的成员之一，是一种有效的逆转录病毒限制因子，具有抗HIV活性。在这里，我们描述了可能是人类基因组中最年轻的TRIM基因。例如，我们已经确定了11个TRIM基因是人类和非洲猿类（黑猩猩、倭黑猩猩和大猩猩）特有的，另外7个是人类特有的。这些年轻的基因中有许多从未被描述过，它们的鉴定使已知的人类TRIM基因总数达到大约100个。这些基因是通过片段复制获得的，其中大部分来自11号染色体上的单个位点。该基因座的另一个多态复制导致这些基因在人群中的拷贝数可变，与本研究筛选的其他个体相比，一名汉族妇女被鉴定出这些TRIM基因的12个额外拷贝。最近，该位点被标注为黑猩猩和恒河猴基因组中34个拷贝数可变的“热点”区域之一。大多数来自该位点的年轻TRIM基因在已知的决定TRIM5α病毒识别的区域表达、剪接并包含积极自然选择的特征。然而，我们发现它们不限制与TRIM5α相同的逆转录病毒，这与在控制靶特异性的区域观察到的高度分化一致。我们提出，这种重组挥发位点作为一个储存库，通过片段复制产生新的TRIM基因，使灵长类动物能够不断获得新的抗病毒基因，这些基因可以被选择用于靶向新的和进化的病原体。生物学中的一个基本问题是免疫系统如何能够使它面对的大量病原体失活。绝大多数病原体很快被先天免疫系统中和，先天免疫系统是一个庞大的防御网络，大约占人类基因组的1/30。因为病原体总是在进化，这些先天免疫基因必须能够获得新的特异性。在这里，我们展示了一种新的进化机制，这种机制已被TRIM先天免疫基因大家族所采用。我们在第11号染色体上发现了一组串联排列的TRIM基因，作为一个“储存库”，新的TRIM基因不断从中产生。我们发现，这个基因簇容易产生自身的复制，从而允许灵长类动物基因组不断获得新的TRIM基因拷贝，这些基因拷贝可能被选择来对抗现有的和新的病原体。
Tripartite Motif (TRIM) ubiquitin ligases act in the innate immune response against viruses. One of the best characterized members of this family, TRIM5α, serves as a potent retroviral restriction factor with activity against HIV. Here, we characterize what are likely to be the youngest TRIM genes in the human genome. For instance, we have identified 11 TRIM genes that are specific to humans and African apes (chimpanzees, bonobos, and gorillas) and another 7 that are human-specific. Many of these young genes have never been described, and their identification brings the total number of known human TRIM genes to approximately 100. These genes were acquired through segmental duplications, most of which originated from a single locus on chromosome 11. Another polymorphic duplication of this locus has resulted in these genes being copy number variable within the human population, with a Han Chinese woman identified as having 12 additional copies of these TRIM genes compared to other individuals screened in this study. Recently, this locus was annotated as one of 34 “hotspot” regions that are also copy number variable in the genomes of chimpanzees and rhesus macaques. Most of the young TRIM genes originating from this locus are expressed, spliced, and contain signatures of positive natural selection in regions known to determine virus recognition in TRIM5α. However, we find that they do not restrict the same retroviruses as TRIM5α, consistent with the high degree of divergence observed in the regions that control target specificity. We propose that this recombinationally volatile locus serves as a reservoir from which new TRIM genes arise through segmental duplication, allowing primates to continually acquire new antiviral genes that can be selected to target new and evolving pathogens. A fundamental question in biology is how the immune system is able to inactivate the enormous number of pathogens that it faces. The vast majority of pathogens are quickly neutralized by the innate immune system, a large network of defenses to which approximately 1/30 of the human genome is devoted. Because pathogens are always evolving, these innate immunity genes must be able to acquire new specificities. Here we illustrate a novel mechanism of evolution that has been employed by the large family of TRIM innate immunity genes. We have found a cluster of tandemly arranged TRIM genes on chromosome 11 that serves as a “reservoir” from which new TRIM genes constantly arise. We show that this gene cluster is prone to spawning duplications of itself, allowing primate genomes to continually acquire new TRIM gene copies that can presumably be selected to combat present and new pathogens.
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