A synchronized global sweep of the internal genes of modern avian influenza virus.
A synchronized global sweep of the internal genes of modern avian influenza virus.
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流感等人畜共患传染病继续对人类健康构成严重威胁。然而，介导甲型流感病毒（IVA）等RNA病毒出现的因素仍不完全清楚。系统发育推断对于重建起源和追踪甲型流感病毒在宿主内部和宿主之间的流动至关重要。在这里，我们表明明确允许IVA宿主谱系具有独立的分子进化速率是可靠的IVA系统发育推断所必需的，而不这样做的方法，包括“宽松”分子钟模型，可能会产生误导。一项使用宿主特异性本地时钟模型的系统基因组学分析在所有基因组片段中恢复了极其一致的进化历史，并证明马H7N7谱系是来自鸟类的菌株的姐妹分支——以及来自人类、猪和马H3N8谱系的菌株——在19世纪中后期与它们共享一个祖先。此外，西半球和东半球的主要禽流感谱系在19世纪后期的每次基因合并中推断出来。基于这些系统发育和这些关键节点的同同性，我们推断禽流感病毒（AIV）的内部基因从19世纪末开始经历了一次全球选择性清除，这一过程一直持续到整个20世纪直到现在。由此产生的西半球AIV谱系随后为1918年大流行病毒和1963年马H3N8流行性兽疫谱系贡献了大部分基因组片段。这种方法为IVA进化模式和过程提供了令人惊讶的清晰解决方案，包括病毒基因和基因组在宿主谱系内部和之间的流动。
Zoonotic infectious diseases such as influenza continue to pose a grave threat to human health. However, the factors that mediate the emergence of RNA viruses like influenza A virus (IVA) remain incompletely understood. Phylogenetic inference is crucial to reconstructing the origins and tracing the flow of influenza A virus within and between hosts. Here, we show that explicitly allowing IVA host lineages to have independent rates of molecular evolution is necessary for reliable phylogenetic inference of IVA and that methods that do not do so, including ‘relaxed’ molecular clock models, can positively mislead. A phylogenomic analysis using a host-specific local clock model recovers extremely consistent evolutionary histories across all genomic segments and demonstrates that the equine H7N7 lineage is a sister clade to strains from birds—as well as those from humans, swine, and the equine H3N8 lineage— sharing an ancestor with them in the mid- to late-1800s. Moreover, major Western and Eastern Hemisphere avian influenza lineages inferred for each gene coalesce in the late 1800s. Based on these phylogenies and the synchrony of these key nodes, we infer that the internal genes of avian influenza virus (AIV) underwent a global selective sweep beginning in the late 1800s, a process that continued throughout the 20th century and up to the present. The resulting western hemispheric AIV lineage subsequently contributed most of the genomic segments to the 1918 pandemic virus and, independently, the 1963 equine H3N8 panzootic lineage. This approach provides a surprisingly clear resolution of IVA evolutionary patterns and processes, including the flow of viral genes and genomes within and between host lineages.