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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Simultaneous amino acid substitutions at antigenic sites drive influenza A hemagglutinin evolution
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Simultaneous amino acid substitutions at antigenic sites drive influenza A hemagglutinin evolution

机译：抗原位点的同时氨基酸置换驱动甲型流感血凝素进化

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摘要

The HA1 domain of HA, the major antigenic protein of influenza A viruses, contains all of the antigenic sites of HA and is under continual immune-driven selection. To resolve controversies on whether only a few or many residue sites of HA1 have undergone positive selection, whether positive selection at HA1 is continual or punctuated, and whether antigenic change is punctuated, we introduce an approach to analyze 2, 248 HA1 sequences collected from 1968 to 2005. We identify 95 substitutions at 63 sites from 1968 to 2005 and show that each substitution occurred very rapidly. The rapid substitution and the fact that 57 of the 63 sites are antigenic sites indicate that hitchhiking plays a minor role and that most of these sites, many more than previously found, have undergone positive selection. Strikingly, 88 of the 95 substitutions occurred in groups, and multiple mutations at antigenic sites sped up the fixation process. Our results suggest that positive selection has been ongoing most of the time, not sporadic, and that multiple mutations at antigenic sites cumulatively enhance antigenic drift, indicating that antigenic change is less punctuated than recently proposed.
机译：HA的HA1结构域（A型流感病毒的主要抗原蛋白）包含HA的所有抗原位点，并且处于持续的免疫驱动选择之下。为了解决关于仅对HA1的几个残基位点进行正选择，对HA1的正选择是连续的还是被标记的以及是否对抗原的变化进行标记的争论，我们引入了一种方法来分析从1968年收集的2,248个HA1序列到2005年。我们从1968年到2005年在63个地点鉴定了95个替代，并且表明每个替代都发生得非常快。快速替换以及63个位点中的57个是抗原性位点这一事实表明，搭便车的作用很小，而且这些位点中的大多数（比以前发现的要多得多）已经历了积极的选择。令人惊讶的是，在95个置换中有88个是成组发生的，抗原位点的多个突变加快了固定过程。我们的结果表明，在大多数时间中，阳性选择一直在进行，而不是零星的，而且抗原位点的多个突变可累积增强抗原漂移，这表明与最近提出的相比，抗原变化的标点少。

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