Effects of passage history and sampling bias on phylogenetic reconstruction of human influenza A evolution
Effects of passage history and sampling bias on phylogenetic reconstruction of human influenza A evolution
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DOI：
10.1073/pnas.97.13.6974
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发表时间：
2000-06-20
影响因子：
11.1
通讯作者：
Fitch, WM
中科院分区：
文献类型：
--
作者：
Bush, RM;Smith, CB;Fitch, WM
在本文中，我们确定在何种程度上宿主介导的突变和一个已知的采样偏差影响人类甲型流感的进化研究。先前使用血凝素基因对甲型H3N2流感进化进行的系统发育重建揭示了分配给树的末端分支的过量非沉默取代。我们研究了两种假设来解释这一观察结果，第一种假设是，过量反映了从人类宿主中分离的病毒样本中不存在或频率较低的突变，并且这些突变在病毒在含胚卵中传代期间频率增加。已知经历这种“宿主介导的”突变的一组22个密码子显示出分配给将来自卵培养的（与细胞培养的相反）分离物的序列附着到树的分支的突变显著过量。我们的第二个假设是，剩余的过剩结果抽样偏差。流感监测有目的地偏向于对抗原性不同的毒株进行测序，以识别可能表明需要更新疫苗的新变异。这种偏向性产生了过量的突变分配给末端分支，这仅仅是因为没有近亲的分离物根据定义是通过相对长的分支连接到树上的。模拟显示，我们在血凝素树中观察到的过量突变的幅度与基于我们的采样方案的预期一致。抽样偏差不影响从系统发育分析中得出的进化推论。然而，如果可能的话，宿主介导的突变引起的过量应该从流感病毒在人类宿主中复制时的进化研究中删除。
In this paper we determine the extent to which host-mediated mutations and a known sampling bias affect evolutionary studies of human influenza A. Previous phylogenetic reconstruction of influenza A (H3N2) evolution using the hemagglutinin gene revealed an excess of nonsilent substitutions assigned to the terminal branches of the tree. We investigate two hypotheses to explain this observation, The first hypothesis is that the excess reflects mutations that were either not present or were at low frequency in the viral sample isolated from its human host, and that these mutations increased in frequency during passage of the virus in embryonated eggs. A set of 22 codons known to undergo such "host-mediated" mutations showed a significant excess of mutations assigned to branches attaching sequences from egg-cultured las opposed to cell-cultured) isolates to the tree. Our second hypothesis is that the remaining excess results from sampling bias. Influenza surveillance is purposefully biased toward sequencing antigenically dissimilar strains in an effort to identify new variants that may signal the need to update the vaccine. This bias produces an excess of mutations assigned to terminal branches simply because an isolate with no close relatives is by definition attached to the tree by a relatively long branch. Simulations show that the magnitude of excess mutations we observed in the hemagglutinin tree is consistent with expectations based on our sampling protocol. Sampling bias does not affect inferences about evolution drawn from phylogenetic analyses. However, if possible, the excess caused by host-mediated mutations should be removed from studies of the evolution of influenza viruses as they replicate in their human hosts.