江浙沪地区乙肝病毒B、C基因型S基因突变及选择压力分析  

Mutation and selective pressure of S gene in hepatitis B virus genotypes B & C in Jiangsu-Zhejiang-Shanghai area

作　　者：陈海江[1,2] 崔大伟[1] 余景璐 陈瑜[1] CHEN Haijiang CUI Dawei YU Jinglu CHEN Yu(Department of Laboratory Medicine, the First Affiliated Hospital of Zhejiang University College of Medicine Key Laboratory of Clinical in Vitro Diagnostic Techniques of Zhejiang, Hangzhou, Zhejiang 310003, China)

机构地区：[1]浙江大学医学院附属第一医院检验科,浙江省临床体外诊断技术研究重点实验室,浙江杭州310003 [2]绍兴市妇幼保健院,浙江绍兴312000

出　　处：《中国微生态学杂志》2017年第7期771-775,781,共6页Chinese Journal of Microecology

基　　金：国家科技重大专项“传染病监测技术平台”项目(2012ZX10004-210)

摘　　要：目的系统分析江浙沪三地的乙肝病毒B、C基因型S基因突变和选择压力情况,以期为乙型肝炎的防治提供理论依据。方法采用NCBI数据库提供的乙肝病毒序列,分为B、C基因型两组,分析突变情况,同时采用Datamonkey进行选择压力分析和Bioedit进行氨基酸置换熵值分析。结果S基因226个氨基酸位点突变分析中,产生突变有位点122个,位点突变率C基因型(45.58%)高于B基因型(30.09%)(χ~2=11.523,P=0.001);总突变率C基因型(1.36%)高于B基因型(0.80%)(χ~2=46.642,P=0.000);α决定簇突变率C基因型(2.40%)高于B基因型(0.96%)(χ~2=20.524,P=0.000)。B基因型α决定簇突变率高于总突变率(χ~2=0.735,P=0.391);C基因型α决定簇突变率高于总突变率(χ~2=44.467,P=0.000)。B基因型氨基酸突变最多的位点为200、213、161和21位点,C基因型氨基酸突变最多的位点为126、68、3、53和194位点。两个基因型dN/dS均值均小于1。B基因型没有发现正向选择位点,发现8个负向选择位点。C基因型发现7个正向选择位点,17个负向选择位点。B基因型仅发现一个易突变位点(200位),C基因型也仅发现一个易突变位点(126位),大多数氨基酸位点熵值<0.4。结论江浙沪地区S基因突变率水平较低,其中C基因型位点突变率、α决定簇突变率和总突变率高于B基因型,α决定簇突变率高于总突变率。C基因型经历外界环境免疫选择压力和自身进化压力双重影响,自身进化压力强于外界环境免疫选择压力;而B基因型主要遭受自身进化压力。尤其要格外关注C基因型的进化进程。Objective To systematically analyze the mutation and selective pressure of S gene of hepatitis B virus genotypes B and C in Jiangsu-Zhejiang-Shanghai area,in order to provide theoretical basis for the prevention and treatment of hepatitis B.Methods The sequences of hepatitis B virus were obtained from NCBI database and divided into groups genotype B or genotype C.The mutations were analyzed;selective pressure was detected with Datamonkey,and amino acids permutation entropy with Bioedit.Results 122 mutation sites were found in 226 amino acids;the locus mutation rate（45.58% vs 30.09%,χ^2=11.523,P=0.001）,total mutation rate（1.36% vs 0.80%,χ^2=46.642,P=0.000）andαdeterminant mutation rate（2.40%vs 0.96%,χ^2=20.524,P=0.000）of genotype C were higher than that of genotype B respectively.Theαdeterminant mutation rates of both genotypes were higher than total mutation rate.Most of amino acid mutation sites of genotype B were at the loci 200,213,161 and 21,while those of genotype C at the loci126,68,3,53 and 194.The average dN/dS of both genotypes were less than 1.Genotype B had no positive selection site but 8negative selection sites.Genotype C had 7positive selection sites,and 17 negative selection sites.Genotype B had only one highly mutable site（200）,so did genotype C（126）.The entropy values of the most of amino acid sites were less than 0.4.Conclusion The mutation rate of S gene is low in Jiangsu-Zhejiang-Shanghai area.The locus mutation rate,αdeterminant mutation rate and total mutation rate of genotype C are higher than those of genotype B.Genotype C is suffering immune selection pressure outside and evolutionarypressure inside,the latter being stronger than the former,while genotype B is suffering only its own evolutionary pressure.The evolution process of genotype C should be paid more attention.

关 键 词：乙肝病毒 S基因 α决定簇突 选择压力 氨基酸置换熵值 

分 类 号：R734.2[医药卫生—肿瘤]