Discordant evolution of the adjacent antiretroviral genes TRIM22 and TRIM5 in mammals.
Discordant evolution of the adjacent antiretroviral genes TRIM22 and TRIM5 in mammals.
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DOI：
10.1371/journal.ppat.0030197
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发表时间：
2007-12
期刊：
影响因子：
6.7
通讯作者：
Malik, Harmit S
中科院分区：
文献类型：
--
作者：
Sawyer, Sara L;Emerman, Michael;Malik, Harmit S
TRIM5α为逆转录病毒感染提供了细胞质阻断，一些灵长类动物编码的同源基因对艾滋病毒具有活性。在这里，我们提出了TRIM5基因与其最接近的人类同源基因：TRIM22、TRIM34和TRIM6的进化比较。我们发现，在哺乳动物的进化过程中，TRIM5和TRIM22具有基因扩展和丢失的动态历史。牛的基因组包含一簇扩大的TRIM5基因，没有TRIM22基因，而狗的基因组编码TRIM22，但丢失了TRIM5。相比之下，TRIM6和TRIM34在人类、狗和牛中被严格保存为单基因同源物。对灵长类的更有针对性的分析表明，虽然TRIM6和TRIM34在净化选择下进化，但TRIM22像以前观察到的TRIM5一样在正选择下进化。基于从27个灵长类基因组中获得的TRIM22序列，我们发现TRIM22的正选择大约发生在2300万年前，这可能反映了病原学格局的变化。然而，我们发现作用于TRIM5和TRIM22的正选择进化片段是相互排斥的，在任何给定的灵长类谱系中，通常只有一个基因被正选择。我们解释说，这意味着一个基因的正向选择限制了其邻居的适应性，这可能是由于遗传连锁造成的。最后，我们发现在TRIM5α和TRIM22中被正选择的氨基酸残基位置有显著的一致性，这两种蛋白主要位于B30.2结构域的β2-β3表面环。令人惊讶的是，在多个奶牛TRIM5基因中，这个相同的环也处于正选择之下，这表明这个小的结构环可能是一个跨越1亿年哺乳动物进化的病毒识别基序。固有免疫蛋白TRIM5α对逆转录病毒感染提供了一种进入后的防御，这取决于其识别逆转录病毒衣壳的特定能力。在灵长类动物进化的大部分过程中，TRIM5α与逆转录病毒一直处于遗传冲突之中，其特征是氨基酸变化的速度高于预期，称为正选择。在这里，我们发现TRIM5‘S最接近的人类近亲之一，TRIM22，也在灵长类动物中进行了正选择。然而，我们发现它与TRIM5的紧密连锁导致了一种反相关的正选择模式，灵长类谱系通常在TRIM5或TRIM22中表现出正选择，但不是两者都有。TRIM22中被发现处于正选择状态的氨基酸位置与先前为TRIM5α描述的“抗病毒特异性补丁”非常接近。在其他哺乳动物中，TRIM5和TRIM22的进化似乎同样不一致；牛的基因组包含一组扩大的TRIM5基因，没有TRIM22基因，而狗的基因组编码TRIM22，但丢失了TRIM5。我们的分析突出了TRIM22具有候选固有免疫基因的所有进化特征。
TRIM5α provides a cytoplasmic block to retroviral infection, and orthologs encoded by some primates are active against HIV. Here, we present an evolutionary comparison of the TRIM5 gene to its closest human paralogs: TRIM22, TRIM34, and TRIM6. We show that TRIM5 and TRIM22 have a dynamic history of gene expansion and loss during the evolution of mammals. The cow genome contains an expanded cluster of TRIM5 genes and no TRIM22 gene, while the dog genome encodes TRIM22 but has lost TRIM5. In contrast, TRIM6 and TRIM34 have been strictly preserved as single gene orthologs in human, dog, and cow. A more focused analysis of primates reveals that, while TRIM6 and TRIM34 have evolved under purifying selection, TRIM22 has evolved under positive selection as was previously observed for TRIM5. Based on TRIM22 sequences obtained from 27 primate genomes, we find that the positive selection of TRIM22 has occurred episodically for approximately 23 million years, perhaps reflecting the changing pathogenic landscape. However, we find that the evolutionary episodes of positive selection that have acted on TRIM5 and TRIM22 are mutually exclusive, with generally only one of these genes being positively selected in any given primate lineage. We interpret this to mean that the positive selection of one gene has constrained the adaptive flexibility of its neighbor, probably due to genetic linkage. Finally, we find a striking congruence in the positions of amino acid residues found to be under positive selection in both TRIM5α and TRIM22, which in both proteins fall predominantly in the β2-β3 surface loop of the B30.2 domain. Astonishingly, this same loop is under positive selection in the multiple cow TRIM5 genes as well, indicating that this small structural loop may be a viral recognition motif spanning a hundred million years of mammalian evolution. The intrinsic immunity protein TRIM5α provides a post-entry defense against retroviral infection, which depends on its specific ability to recognize retroviral capsids. TRIM5α has been locked in genetic conflict with retroviruses throughout most of primate evolution, characterized by a higher than expected rate of amino acid change, referred to as positive selection. Here, we find that one of TRIM5's closest human paralogs, TRIM22, has also undergone positive selection in primates. However, we find that its close linkage to TRIM5 has resulted in an anti-correlated pattern of positive selection, with primate lineages generally showing positive selection in either TRIM5 or TRIM22, but not both. Amino acid positions in TRIM22 found to be under positive selection are in remarkable proximity to the “antiviral specificity patch” previously described for TRIM5α. TRIM5 and TRIM22 evolution appears to be equally discordant in other mammals; the cow genome contains an expanded cluster of TRIM5 genes and no TRIM22 gene, while the dog genome encodes TRIM22 but has lost TRIM5. Our analyses highlight TRIM22 as bearing all the evolutionary hallmarks of a candidate intrinsic immunity gene.