Positive evolutionary selection on the RIG-I-like receptor genes in mammals.
Positive evolutionary selection on the RIG-I-like receptor genes in mammals.
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DOI：
10.1371/journal.pone.0081864
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Esteves PJ
中科院分区：
文献类型：
--
作者：
Lemos de Matos A;McFadden G;Esteves PJ
哺乳动物 RIG-I 样受体 RIG-I、MDA5 和 LGP2 是 DExD/H 盒 RNA 解旋酶家族，负责病毒 RNA 的细胞质检测。这些受体可检测多种 RNA 病毒或表达异常 RNA 种类的 DNA 病毒，其中许多病毒会导致大量严重和致命的疾病。参与病原体识别的宿主先天哨兵蛋白必须在与病原体的动态军备竞赛中快速进化，因此要承受长期的正选择压力以避免潜在的感染。使用六种基于密码子的最大似然方法，我们能够在这三个基因中的每一个中识别出正选择下的特定密码子。在 MDA5 中检测到的阳性选择密码子数量最多，但这些密码子中有很大一部分位于 MDA5 当前定义的蛋白质结构域之外，这可能反映了功能和结构限制的施加。此外，我们的结果支持 LGP2 最不容易发生进化变化，因为观察到该基因的选择密码子数量最少。另一方面，在已知的蛋白质功能域中检测到了 RIG-I 阳性选择密码子的优势，这表明这种 RNA 解旋酶识别的大量病毒施加了压力。此外，RIG-I阻遏结构域（负责识别并结合其RNA底物的区域）表现出最有力的选择压力证据。进行了分支位点分析，三个受体基因树上的几个物种分支显示了间歇性正选择的证据。总之，通过寻找哺乳动物 RIG-I 样受体基因正向进化选择的证据，我们提出多种病毒在宿主防御中精心设计了受体生物学功能，特别是 RIG-I 基因，有助于对不同病毒病原体的先天物种特异性抵抗/易感性。
The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H box RNA helicases responsible for the cytoplasmic detection of viral RNA. These receptors detect a variety of RNA viruses, or DNA viruses that express unusual RNA species, many of which are responsible for a great number of severe and lethal diseases. Host innate sentinel proteins involved in pathogen recognition must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected to long-term positive selection pressures to avoid potential infections. Using six codon-based Maximum Likelihood methods, we were able to identify specific codons under positive selection in each of these three genes. The highest number of positively selected codons was detected in MDA5, but a great percentage of these codons were located outside of the currently defined protein domains for MDA5, which likely reflects the imposition of both functional and structural constraints. Additionally, our results support LGP2 as being the least prone to evolutionary change, since the lowest number of codons under selection was observed for this gene. On the other hand, the preponderance of positively selected codons for RIG-I were detected in known protein functional domains, suggesting that pressure has been imposed by the vast number of viruses that are recognized by this RNA helicase. Furthermore, the RIG-I repressor domain, the region responsible for recognizing and binding to its RNA substrates, exhibited the strongest evidence of selective pressures. Branch-site analyses were performed and several species branches on the three receptor gene trees showed evidence of episodic positive selection. In conclusion, by looking for evidence of positive evolutionary selection on mammalian RIG-I-like receptor genes, we propose that a multitude of viruses have crafted the receptors biological function in host defense, specifically for the RIG-I gene, contributing to the innate species-specific resistance/susceptibility to diverse viral pathogens.
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DOI：
10.3109/10409238.2011.630974
发表时间：
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影响因子：
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作者：
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通讯作者：
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