Abstract Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare at the between-host scale. Here, we compare the genetic variation of H3N2 influenza within and between hosts to link viral evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted between hosts compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that act on within-host variants of influenza virus as they transmit and circulate between hosts.

中文翻译：

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将人类宿主内部和之间的流感病毒进化联系起来

摘要 流感病毒在个体人类感染中迅速多样化。最近的几项研究对临床流感感染进行了深度测序，以确定宿主内的病毒变异，但尚不清楚宿主内突变在宿主间规模上的表现。在这里，我们比较了宿主内部和宿主之间 H3N2 流感的遗传变异，以将病毒进化动力学跨尺度联系起来。同义位点在两个尺度上以相似的速率进化，表明这些假定中性位点的全球进化是由宿主内变异的积累造成的。然而，与宿主内部相比，宿主之间的非同义突变被耗尽，这表明选择清除了宿主内部出现的许多蛋白质改变变化。例外是在抗原位点，其中选择可检测到有利于全球范围内的非同义突变，但不在宿主内。这些结果表明，当流感病毒在宿主之间传播和循环时，针对有害突变的选择和对抗原变化的选择是作用于流感病毒宿主内变体的主要力量。