H3N2亚型人甲型流感病毒HA1序列进化正向选择位点研究

许慧琳; 张文彤; 赵耐青; 姜庆五

Abstract

许慧琳,张文彤,赵耐青,姜庆五.H3N2亚型人甲型流感病毒HA1序列进化正向选择位点研究[J].Chinese journal of Epidemiology,2007,28(4):385-389

H3N2亚型人甲型流感病毒HA1序列进化正向选择位点研究

Study on the detection of positive selected codons on HA1 sequence of human influenza A subtype H3N2

Received:September 22, 2006

DOI：

KeyWord: 甲型流感病毒亚型，H3N2 正向选择位点

English Key Word: Innuenza virus type A Subtype,H3N2 Positive selected codons

FundProject:国家自然科学基金资助项目(30400370)

Author Name	Affiliation	E-mail
XU Huilin	Department of Health Statistics and Social Medicine, School of Public Health, Fudan University, Shanghai 200032, China
ZHANG Wentong	Department of Health Statistics and Social Medicine, School of Public Health, Fudan University, Shanghai 200032, China	wtzllang@shmu．edu．cn
ZHAO Naiqing	Department of Health Statistics and Social Medicine, School of Public Health, Fudan University, Shanghai 200032, China
JIANG Qingwu	200032, 上海, 复旦大学公共卫生学院流行病学教研室

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Abstract:

目的<\b> 筛选H3N2亚型人甲型流感病毒红细胞凝聚素(HA1)序列中的正向选择位点,为进一步揭示流感病毒的变异规律.方法<\b> 从NCBI GenBank和流感数据库中下载甲型流感病毒H3亚型RNA4节段序列,用两步聚类法将全部序列分为6个年代类别,使用固定效应似然比检验模型分别筛选每一类中的正向选择位点,并使用两步聚类法归纳所筛选出位点的正向选择压力变化模式.结果<\b> 各年代类别筛选出的正向选择位点不完全相同,共有50个位点在进化过程中经历过正向选择,其中有42个位点属于5个抗原决定簇之一,A、B抗原决定簇在各年代均有较多的位点入选,且承受较大的免疫选择压力.50个位点可被归纳为7种变化模式,前6种模式的位点依次在某一个时间段存在正向选择,第7种模式则在多个年代中均存在正向选择.结论<\b> 分析结果<\b>提示流感病毒HA1序列在进化过程中的正向选择位点并非恒定,而是在不同年代中存在更替趋势.抗原决定簇A、B的变异在流感进化过程中起关键作用,8个位于非抗原决定簇正向选择位点有可能是未被识别的抗原决定簇位点.

English Abstract:

Objective<\b> To elucidate the evolution pattem of human innuellza virus A H3 subtype by detecting positive selected codonS in hemagglutinin gene.Methods<\b> ～1 H3 sequenceS in NCBI GenBank and innuenza sequence database were downloaded and two step cluster method was applied to divide sequences into six groups，which were corresponding to di“erent period by turns.Fixed Effect Model was appIied to detect positive seiected oodons in each group，and two step cluster method was then used again to summarize variation pattems of selective preSsure among sites.Results<\b> Positive selected codons were different in groups corresponding different periods.50 amino acid codons had been identified as positive selected sites in at least one time span.Among them，42 codons belonged to one of the five known antigen- combining regions.A larger amount of sites as well as relatively higher selection pressure were identified in antibody combining regions A and B.Results<\b> showed that the 50 sites could be divided into seven different pattems.While other six patterns corresponding to positive selected codons at only one time span，the sites of the seventh pattem were under positive selection in several periods.Conclusion<\b> Positive selection codons in evolution of H3A1 strains were alternated in different time period whereas antibody combining regions A and B played more important roles in the evoIution process.0ther 8 identified codons out of the antibOdy combining regions might belong to unknown antigen regions.

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