High Meadows Environmental Institute, Princeton University, Princeton, NJ, United States of America; Department of Science and Environment, Roskilde University, Roskilde, Denmark; Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.
Department of Science and Environment, Roskilde University, Roskilde, Denmark.
Theor Popul Biol. 2024 Oct;159:25-34. doi: 10.1016/j.tpb.2024.07.005. Epub 2024 Jul 31.
Leveraging the simplicity of nucleotide mismatch distributions, we provide an intuitive window into the evolution of the human influenza A 'nonstructural' (NS) gene segment. In an analysis suggested by the eminent Danish biologist Freddy B. Christiansen, we illustrate the existence of a continuous genetic "backbone" of influenza A NS sequences, steadily increasing in nucleotide distance to the 1918 root over more than a century. The 2009 influenza A/H1N1 pandemic represents a clear departure from this enduring genetic backbone. Utilizing nucleotide distance maps and phylogenetic analyses, we illustrate remaining uncertainties regarding the origin of the 2009 pandemic, highlighting the complexity of influenza evolution. The NS segment is interesting precisely because it experiences less pervasive positive selection, and departs less strongly from neutral evolution than e.g. the HA antigen. Consequently, sudden deviations from neutral diversification can indicate changes in other genes via the hitchhiking effect. Our approach employs two measures based on nucleotide mismatch counts to analyze the evolutionary dynamics of the NS gene segment. The rooted Hamming map of distances between a reference sequence and all other sequences over time, and the unrooted temporal Hamming distribution which captures the distribution of genotypic distances between simultaneously circulating viruses, thereby revealing patterns of nucleotide diversity and epi-evolutionary dynamics.
利用核苷酸错配分布的简单性，我们提供了一个直观的窗口，了解人类流感 A 型“非结构”（NS）基因片段的进化。在丹麦杰出生物学家 Freddy B. Christiansen 提出的分析中，我们说明了流感 A NS 序列存在连续的遗传“主干”，在一个多世纪的时间里，核苷酸距离不断增加，与 1918 年的根距离越来越远。2009 年的甲型 H1N1 流感大流行显然偏离了这一持久的遗传主干。利用核苷酸距离图和系统发育分析，我们说明了关于 2009 年大流行起源的剩余不确定性，突出了流感进化的复杂性。NS 片段之所以有趣，正是因为它经历的广泛正选择较少，与例如 HA 抗原相比，偏离中性进化的程度较小。因此，突然偏离中性多样化可能表明其他基因通过搭便车效应发生了变化。我们的方法采用了两种基于核苷酸错配计数的措施来分析 NS 基因片段的进化动态。基于根的哈明距离图显示了参考序列与随时间推移的所有其他序列之间的距离，以及无根的时间哈明分布，它捕获了同时循环的病毒之间基因型距离的分布，从而揭示了核苷酸多样性和进化动态的模式。
