Long term trends in the evolution of H(3) HA1 human influenza type A
Long term trends in the evolution of H(3) HA1 human influenza type A
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DOI：
10.1073/pnas.94.15.7712
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发表时间：
1997-07-22
影响因子：
11.1
通讯作者：
Cox, NJ
中科院分区：
文献类型：
--
作者：
Fitch, WM;Bush, RM;Cox, NJ
我们研究了254个人甲型流感（H3 N2）病毒基因的HA 1结构域，以寻找可能有助于识别循环毒株血凝素（HA）特征的线索，这些特征可预测该毒株的流行潜力。我们的初步调查结果包括以下内容。(i)发现的最简约的树需要1，260个替换，其中712个是沉默的，548个是替换替换。(ii)HA基因的HA 1部分以每年5.7个核苷酸替换或每年5.7 × 10（-3）个替换/位点的速率进化。(iii)当考虑到每个密码子可以改变编码的氨基酸的方式的数量时，置换取代随机分布在密码子的三个位置上。(iv)替换不是随机分布在树的分支上，每个尖端分支的变化是非尖端分支的2.2倍。该结果与测序前病毒的扩增方式（卵细胞生长或肾细胞生长）或是否通过PCR直接对原始临床标本进行测序无关。(v)尖端分支上的这些过度变化可能是选择测序菌株的偏差以及检测到尚未通过负选择去除的有害突变的结果。(vi)有6个高变密码子以平均7.2倍于其他变异密码子的速率积累替换替换。(vii)主干分支（与免疫系统竞争的获胜者）中可变密码子的数量为47 +/-5，显著少于细枝（90 +/-7），细枝又显著少于梢部分支（175 +/-8）中的可变密码子。（viii）每12个分支中至少有一个分支在两端具有代表居住在不同大陆的病毒的节点。然而，如果随机重新分配分离株的起源大陆，这并不比预期的多。(ix)在99个至少有4个突变的密码子中，31个密码子的非沉默与沉默变化的比率小于0.05，其中14个密码子的概率小于0.05。
We have studied the HA1 domain of 254 human influenza A(H3N2) virus genes for clues that might help identify characteristics of hemagglutinins (HAs) of circulating strains that are predictive of that strain's epidemic potential. Our preliminary findings include the following. (i) The most parsimonious tree found requires 1,260 substitutions of which 712 are silent and 548 are replacement substitutiions. (ii) The HA1 portion of the HA gene is evolving at a rate of 5.7 nucleotide substitutions/year or 5.7 X 10(-3) substitution/site per year. (iii) The replacement substitutions are distributed randomly across the three positions of the codon when allowance is made for the number of ways each codon can change the encoded amino acid. (iv) The replacement substitutions are not distributed randomly over the branches of the tree, there being 2.2 times more changes per tip branch than for non-tip branches. This result is independent of how the virus was amplified (egg grown or kidney cell grown) prior to sequencing or if sequencing was carried out directly on the original clinical specimen by PCR. (v) These excess changes on the tip branches are probably the result of a bias in the choice of strains to sequence and the detection of deterious mutations that had not yet been removed by negative selection. (vi) There are six hypervariable codons accumulating replacement substitutions at an an average rate that is 7.2 times that of the other varied codons. (vii) The number of variable codons in the trunk branches (the winners of the competitive race against the immune system) is 47 +/- 5, significantly fewer than in the twigs (90 +/- 7), which in turn is significantly fewer variable codons than in tip branches (175 +/- 8). (viii) A minimum of one of every 12 branches has nodes at opposite ends representing viruses that reside on different continents. This is, however, no more than would be expected if one were to randomly reassign the continent of origin of the isolates. (ix) Of 99 codons with at least four mutations, 31 have ratios of non-silent to silent changes with probabilities less than 0.05 of occurring by chance, and 14 of those have probabilities