Positive natural selection in primate genes of the type I interferon response.
Positive natural selection in primate genes of the type I interferon response.
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DOI：
10.1186/s12862-021-01783-z
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发表时间：
2021-04-26
影响因子：
2.2
通讯作者：
Sawyer SL
中科院分区：
文献类型：
--
作者：
Judd EN;Gilchrist AR;Meyerson NR;Sawyer SL
I型干扰素反应是对抗病毒的重要一线防御。反过来，病毒拮抗（即，降解，错定位等）干扰素途径中的许多蛋白质。因此，宿主和病毒被锁定在一场进化军备竞赛中，以争夺I型干扰素途径的优势。因此，干扰素途径中的许多基因经历了积极的自然选择，有利于新的等位基因形式，可以更好地识别病毒或逃避病毒拮抗剂。在这里，我们对作用于I型干扰素家族基因的选择压力进行了全面分析。我们最初假设，负责诱导干扰素产生的基因比因干扰素而激活的基因更容易被病毒拮抗。我们的逻辑是，如果病毒在干扰素分子产生的上游工作，它们将产生更大的影响，因为一旦干扰素产生，数百种受干扰素刺激的蛋白质将被激活，病毒需要一个接一个地抵消它们。我们对131个在干扰素产生和信号传导中活跃的基因（这里称为“诱导”基因）、100个干扰素刺激基因和100个随机选择的基因进行了多次序列比对。我们分析了每个多序列比对的特征，反复阳性选择。与我们的假设相反，我们发现干扰素刺激基因，而不是干扰素诱导基因，比随机的一组基因进化得快得多。干扰素诱导基因以一种与一组匹配的随机基因无法区分的方式进化（分别有22%和18%的基因具有积极选择的特征）。相比之下，受干扰素刺激的基因进化方式不同，33%的基因在正向选择下进化，并且含有更高比例的密码子，这些密码子经历了反复替换编码氨基酸的选择。病毒可能更频繁地对抗干扰素反应的个别产物，而不是试图中和整个系统。在线版本包含补充材料，可在10.1186/s12862-021-01783-z获得。
The Type I interferon response is an important first-line defense against viruses. In turn, viruses antagonize (i.e., degrade, mis-localize, etc.) many proteins in interferon pathways. Thus, hosts and viruses are locked in an evolutionary arms race for dominance of the Type I interferon pathway. As a result, many genes in interferon pathways have experienced positive natural selection in favor of new allelic forms that can better recognize viruses or escape viral antagonists. Here, we performed a holistic analysis of selective pressures acting on genes in the Type I interferon family. We initially hypothesized that the genes responsible for inducing the production of interferon would be antagonized more heavily by viruses than genes that are turned on as a result of interferon. Our logic was that viruses would have greater effect if they worked upstream of the production of interferon molecules because, once interferon is produced, hundreds of interferon-stimulated proteins would activate and the virus would need to counteract them one-by-one. We curated multiple sequence alignments of primate orthologs for 131 genes active in interferon production and signaling (herein, “induction” genes), 100 interferon-stimulated genes, and 100 randomly chosen genes. We analyzed each multiple sequence alignment for the signatures of recurrent positive selection. Counter to our hypothesis, we found the interferon-stimulated genes, and not interferon induction genes, are evolving significantly more rapidly than a random set of genes. Interferon induction genes evolve in a way that is indistinguishable from a matched set of random genes (22% and 18% of genes bear signatures of positive selection, respectively). In contrast, interferon-stimulated genes evolve differently, with 33% of genes evolving under positive selection and containing a significantly higher fraction of codons that have experienced selection for recurrent replacement of the encoded amino acid. Viruses may antagonize individual products of the interferon response more often than trying to neutralize the system altogether. The online version contains supplementary material available at 10.1186/s12862-021-01783-z.
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