Variation and Evolution in Plants and Microorganisms Toward a New Synthesis 50 Years After Stebbins (2000) / Chapter Skim
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6 Effects of Passage History and Sampling Bias on Phylogenetic Reconstruction of Human Influenza A Evolution
6 Effects of Passage History and Sampling Bias on Phylogenetic Reconstruction of Human Influenza A Evolution
Pages 83-98
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From page 83... ...
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.
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From page 84... ...
Here we determine the extent to which HM mutations and a known sampling bias affect studies of influenza A evolution. Recent phylogenetic reconstruction of the evolution of human influenza A hemagglutinin (HA)
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From page 85... ...
Phylogenetic Reconstruction of Human Influenza A Evolution / 85 rT {A 1 ~ Al FIGURE 1. Maximum parsimony tree constructed from 357 HA1 genes of the human influenza virus type A subtype H3.
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From page 86... ...
There is thus great potential for error in inference if one assumes that HM mutations reflect evolution of influenza viruses within the human host. Here we test for the presence of HM mutations in our data set by examining the distribution of mutations in the HM and non-HM codons between branches attaching sequences from egg-cultured and cellcultured isolates to the tree.
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From page 87... ...
The tree on the right is a reconstruction after (i) sampling only eight of the viruses with a bias against sequencing closely related isolates and (ii)
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From page 88... ...
TABLE 1. Codons known to undergo HM mutations during propagation in egg culture Codon Rbs AB PosSel 111 0 0 0 126 0 1 0 137 1 1 0 138 1 1 1 144 0 1 0 145 0 1 1 155 1 1 0 156 0 1 1 158 0 1 1 159 0 1 0 185 0 0 0 186 0 1 1 193 0 1 1 194 1 1 1 199 0 0 0 219 0 0 0 226 1 0 1 229 0 0 0 246 0 0 0 248 0 0 0 276 0 0 0 290 0 0 0 Five of the 22 HM codons known to undergo HM mutations during propagation in egg culture are associated with the HA sialic acid receptor binding site (Rbs)
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From page 89... ...
. We refer to these 22 codons as the HM codons and the other 307 codons as the non-HM codon set.
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From page 90... ...
We retain the assignment procedure that minimizes the number of mutations assigned to the terminal branches for all analyses that follow. HYPOTHESIS 1: HM MUTATIONS We first determined whether there was evidence that HM mutations were contributing to the excess nonsilent substitutions on the terminal branches of the HA tree.
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From page 91... ...
Second, we determined whether there were any additional codons, besides the 22 in the HM set, that showed evidence for undergoing HM mutations. HM Mutations in the Egg and Cell Branches If HM mutations were occurring in the 22 HM codons, then we should see excess mutations in the HM codons on the egg branches, or the terminal branches attaching sequences from egg-cultured isolates to the tree (Fig.
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From page 92... ...
Based on this analysis we find no evidence to support the hypothesis that codons in addition to the 22 in the HM codon set are undergoing HM mutations during laboratory passage unless they are doing so at the same rate at which they undergo mutations in response to passage in cell culture. HYPOTHESIS 2: SAMPLING BIAS We have shown that HM mutations in the 22 HM codons appear to be responsible for some of the excess mutations on the terminal branches of the HA1 tree in Fig.
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From page 93... ...
substitutions on trees constructed using only sequences from egg-cultured or cellcultured isolates and using only non-HM codons Number of branches Exp NS Obs NS x2 Branches on egg tree Terminal 152 119.3 155 10.7 Internal 150 117.7 82 10.8 Total 302 237.0 237 21.5 Branches on cell tree Terminal 148 121.3 158 11.1 Internal 146 119.7 83 11.2 Total 294 241.0 241 22.3 Trees constructed without the HM codons using sequences from isolates propagated in egg culture or in cell culture both showed significant excesses of nonsilent substitutions on their terminal branches (P < 0.05, df = 1 for both tests)
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From page 94... ...
Bush et al. total population r{ I{ _ { 1{ L{ by{ {I 0% excess mutations on terminal branches 25 20Sum of Branch 15Lengths 105Odispersed sub-sample F _ ~ 4- ~~x'x{_ _ -- xi.., ~ _ re Toe clumped sub-sample r I' ax I- fix at x_ ~ ~ me % excess = 27% % excess = 14% % excess = 3% % deficit = 13% All Branches slope = - 2.0 Terminal Branches slope = - 2.7 Internal Branches slope= 0.7 —~ -- - - ~ Values for Trees Shown Above FIGURE 3.
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From page 95... ...
The 59 apparently HM mutations represent 7.9% of the 745 nonsilent substitutions that occurred over the time period sampled. Thus, there is good reason for concern about HM mutations if one wants to draw inferences about evolution from this or any similarly affected data set.
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From page 96... ...
After fixation of the HM nonsilent substitution, silent substitutions once again would begin to accumulate. Because we do not know the exact circumstances under which HM mutations occurred in our data set relative to the time at which particular isolates were sequenced, we cannot make any predictions about the relative frequencies of nonsilent or silent substitutions in the HM codons as compared with the non-HM codons.
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From page 97... ...
The observation of excess mutations assigned to the terminal branches of the HA tree is consistent with expectations based on two very different hypotheses. HM mutations appear to account for part of the excess.
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From page 98... ...
(1993) Clinical influenza virus and the embryonated hen's egg.
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