Using Non-Homogeneous Models of Nucleotide Substitution to Identify Host Shift Events: Application to the Origin of the 1918 'Spanish' Influenza Pandemic Virus
Using Non-Homogeneous Models of Nucleotide Substitution to Identify Host Shift Events: Application to the Origin of the 1918 'Spanish' Influenza Pandemic Virus
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DOI：
10.1007/s00239-009-9282-x
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发表时间：
2009-10-01
影响因子：
3.9
通讯作者：
Goldstein, Richard A.
中科院分区：
文献类型：
--
作者：
dos Reis, Mario;Hay, Alan J.;Goldstein, Richard A.
核苷酸取代的非齐次马尔可夫模型很少受到关注。在这里，我们探讨了使用非同质模型，以确定主机移位节点沿着在不同的主机中进化的病原体的系统发育树的可能性。已经注意到，流感病毒在人和禽宿主中显示出核苷酸组成的显著差异。我们利用这一事实来确定导致1918年“西班牙”流感的宿主转移事件。这种疾病在全世界造成5 000多万人死亡，是有史以来最致命的大流行病。我们的模型表明，最终成为1918年病毒基因组的八个RNA片段是在1882-1913年左右引入哺乳动物宿主的。这些病毒后来在1913年至1915年左右分化成经典的猪和人类H1N1流感谱系。人类菌株的最后共同祖先可以追溯到1917年2月至1918年4月。由于猪比人类更容易感染禽流感病毒，因此它们似乎是病毒的原始接受者。这表明该病毒是在1913年至1918年之间的某个时候被引入人类的。
Nonhomogeneous Markov models of nucleotide substitution have received scant attention. Here we explore the possibility of using nonhomogeneous models to identify host shift nodes along phylogenetic trees of pathogens evolving in different hosts. It has been noticed that influenza viruses show marked differences in nucleotide composition in human and avian hosts. We take advantage of this fact to identify the host shift event that led to the 1918 'Spanish' influenza. This disease killed over 50 million people worldwide, ranking it as the deadliest pandemic in recorded history. Our model suggests that the eight RNA segments which eventually became the 1918 viral genome were introduced into a mammalian host around 1882-1913. The viruses later diverged into the classical swine and human H1N1 influenza lineages around 1913-1915. The last common ancestor of human strains dates from February 1917 to April 1918. Because pigs are more readily infected with avian influenza viruses than humans, it would seem that they were the original recipient of the virus. This would suggest that the virus was introduced into humans sometime between 1913 and 1918.