Calibration of multiple poliovirus molecular clocks covering an extended evolutionary range
Calibration of multiple poliovirus molecular clocks covering an extended evolutionary range
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DOI：
10.1128/jvi.02354-07
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发表时间：
2008-05-01
影响因子：
5.4
通讯作者：
Kew, Olen
中科院分区：
文献类型：
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作者：
Jorba, Jaume;Campagnoli, Ray;Kew, Olen
我们根据 P1/衣壳区域（2,643 个核苷酸）的总替换 (K-t)、同义替换 (K-s)、同义转换 (A(s))、同义颠换 (B-s) 和非同义替换 (K-a) 的固定率，校准了循环脊髓灰质炎病毒的五种不同分子钟。通过分析 31 种野生 1 型脊髓灰质炎病毒分离株的序列，确定了 10 年期间的发病率，这些分离株代表了源自共同输入祖先的明确系统发育。通过线性回归、最大似然/单率日期提示方法和贝叶斯推理获得了类似的比率。非常快的 K-t [(1.03 +/- 0.10) x 10(-2) 替换/站点/年] 和 K-s [(1.00 +/- 0.08) x 10(-2)] 时钟主要由 A(s) 时钟 [(0.96 +/- 0.09) x 10(-2)] 驱动，B-s 时钟类似于慢 10 倍[(0.10 +/- 0.03) x 10(-2)]，并且更随机的 K-a 时钟类似于慢 30 倍 [ (0.03 +/- 0.01) x 10(-2)]。所有 P1/衣壳位点（包括中和抗原位点）的非同义取代似乎受到纯化选择的限制。对第三个密码子位置进化的模拟表明，同义转换的饱和在 10 年时会很明显，并在独立传播的 65 年左右完成。同义颠换的饱和度预计在 20 岁时达到最小，并在 100 岁时不完全。 K-t、K-s 和 A(s) 时钟的快速进化可用于估计密切相关病毒的分歧日期，而较慢的 B-s 和 K-a 时钟可用于探索脊髓灰质炎病毒基因型内部和之间更深层次的进化关系。
We have calibrated five different molecular clocks for circulating poliovirus based upon the rates of fixation of total substitutions (K-t), synonymous substitutions (K-s), synonymous transitions (A(s)), synonymous transversions (B-s), and nonsynonymous substitutions (K-a) into the P1/capsid region (2,643 nucleotides). Rates were determined over a 10-year period by analysis of sequences of 31 wild poliovirus type 1 isolates representing a well-defined phylogeny derived from a common imported ancestor. Similar rates were obtained by linear regression, the maximum likelihood/single-rate dated-tip method, and Bayesian inference. The very rapid K-t [(1.03 +/- 0.10) x 10(-2) substitutions/site/year] and K-s [(1.00 +/- 0.08) x 10(-2)] clocks were driven primarily by the A(s) clock [(0.96 +/- 0.09) x 10(-2)], the B-s clock was similar to 10-fold slower [(0.10 +/- 0.03) x 10(-2)], and the more stochastic K-a clock was similar to 30-fold slower [ (0.03 +/- 0.01) x 10(-2)]. Nonsynonymous substitutions at all P1/capsid sites, including the neutralizing antigenic sites, appeared to be constrained by purifying selection. Simulation of the evolution of third-codon positions suggested that saturation of synonymous transitions would be evident at 10 years and complete at similar to 65 years of independent transmission. Saturation of synonymous transversions was predicted to be minimal at 20 years and incomplete at 100 years. The rapid evolution of the K-t, K-s, and A(s) clocks can be used to estimate the dates of divergence of closely related viruses, whereas the slower B-s and K-a clocks may be used to explore deeper evolutionary relationships within and across poliovirus genotypes.