乙型流感病毒Victoria系和Yamagata系HA1基因的分子进化研究

Molecular evolution of two lineages related to influenza B virus based on HA1 gene

目的探讨乙型流感病毒两大谱系的进化特征和进化规律。方法从GenBank数据库下载1940—2012年乙型流感病毒流行株共126条，采用贝叶斯－马尔科夫链－蒙特卡洛（Bayesian—MCMC）和分子钟方法，对乙型流感病毒的HA1基因进行系统发育学分析，计算乙型流感病毒两大谱系可能的起源时问与分化时间。结果1978—2010年乙型流感病毒Victoria系与Yamagata系的aa平均差异率为5．4％～10．2％，两谱系的aa差异和组间遗传距离随时问推移呈逐渐增大的趋势。与Victoria系毒株相比，Yamagata系全部毒株的163位aa及部分毒株的166位aa缺失，但是这些年来的乙型流感病毒HA1基因除个别位点外，尚未受到明显的正向选择压力。每年乙型流感病毒HA1基因的碱基替换速率为2．138×10^-3（95％HPD：1．833×10^-3～2．437×10^-3）替代／位点，推算乙型流感病毒Victoria系和Yamagata系的最近共同祖先出现在1971年（95％HPD：1969—1972年），两大谱系的分化时间点分别为1973年（95％HPD：1971—1974年）和1977年（95％HPD：1975—1978年）。结论乙型流感Victoria系和Yamagata系均较以往发生大的变异，且两大谱系的差异日趋增大，将来有可能分化为不同的亚型，在流感监测中应密切关注这一变化及其流行病学意义。

Objective To study the evolutionary characteristics and rules of two lineages on influenza B virus. Methods A total of 126 HA1 sequences of strains isolated during 1940 to 2012 were downloaded from the GenBank. Time of the most recent common ancestor （TMRCA） and divergence of the two lineages were calculated based on the data from phylogenetic analysis of HA1 gene, using Bayesian Markov Chain Monte Carlo （Bayesian-MCMC） and molecular clock method. Results The average amino acid variant ratios were ranged from 5.4% to 10.2% within the strains of influenza B virus isolated during 1978 to 2010. Compared with the Victoria-like strains, all Yamagata- like strains showed an amino acid deletion at 163^th site, while some of them showing a deletion at position 166. HA1 gene of influenza B virus seemed not have been affected by positive selection except a few sites. The evolutionary average rate on HA1 gene was 2.138 ×10^-3 substitutions/site/year （95%HPD： 1.833 - 10 3-2.437×10^-3 substitutions/site/year）. The estimated dates for TMRCA of the two lineages of influenza B virus could be dated back to 1971 （95% HPD： 1969-1972）, while the divergence times of the two lineages were 1973 （95% HPD： 1971-1974） and 1977 （95% HPD： 1975-1978） respectively. Conclusion Significant differences were found on HA1 gene between earlier and recent identified strains of Victoria and Yamagata lineage. Differences between the two lineages increased and showing the potential of dividing themselves into different subtypes in the future. More attention should be paid to these trends and the related epidemiological significance.