Lu Yi-Han, Ju Li-Wen, Jiang Lu-Fang, Yang Ji-Xing, Shi Qiang, Jiang Qing-Wu
Key Laboratory of Public Health Safety, Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2009 Jul;43(7):553-8.
To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission.
A total of 344 H1 sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution.
It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetically (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57 x 10(-3) substitutions/site per year averagely (95% Highest Posterior Density: 1.96 x 10(-3) - 3.03 x 10(-3)/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46 x 10(-3)/site per year and 0.97 x 10(-3)/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86 x 10(-3)/site per year and 5.02 x 10(-3)/site per year.
The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.
确定近期全球大流行的甲型流感病毒血凝素（HA）基因的进化速率和分歧时间，并探究其起源及传播情况。
收集GenBank中344条H1序列（包括248条人源分离株、84条猪源分离株、11条禽源分离株和1条雪貂源分离株）以及在上海分离的7条序列。基于马尔可夫链蒙特卡罗方法，利用分子钟理论和贝叶斯天际线图（BSP）计算核苷酸替换率和最近共同祖先时间（tMRCA）。然后根据后验分布构建遗传系统发育树。
发现美国的人源、猪源和禽源H1序列在系统发育上与亚洲猪源H1序列显著聚类（美国聚类）。第二个聚类（欧亚人源聚类）几乎由在其他地区分离的人源H1序列组成。第三个聚类（欧亚动物源聚类）分别由来自中国和意大利的猪源和禽源H1序列组成。对于所有H1序列，平均进化速率为每年2.57×10⁻³替换/位点（95%最高后验密度：每年1.96×10⁻³ - 3.03×10⁻³/位点）。欧洲人源H1和中国大陆猪源H₁的tMRCA估计日期最早，相应速率分别为每年6.46×10⁻³/位点和每年0.97×10⁻³/位点。来自美国的人源和猪源H1序列的tMRCA相似，速率分别为每年5.86×10⁻³/位点和每年5.02×10⁻³/位点。
当前流感爆发可能是由甲型流感病毒（H1N1）在美国人群和猪群中的长期传播引起的。没有证据证明中国的流感病毒参与了此次爆发。
