基于NCBI数据库的HBV S基因进化分析

发布时间：2018-03-01 02:34

  本文关键词： HBV S 基因 突变率 进化 选择压力 氨基酸置换熵值　出处：《浙江大学》2017年硕士论文　论文类型：学位论文

【摘要】：研究目的:了解HBV S基因进化特征情况,为乙型肝炎的认知和防治提供新的理论依据。研究方法:选取 NCBI"shanghai"、"zhejiang"、"jiangsu"三地 HBV S 基因序列,共 375 条,分成B和C型两组。首先构建HBVS基因的氨基酸参考序列,然后进行S基因的氨基酸突变情况、遗传多样性动态变化、选择压力及氨基酸置换熵值分析。研究结果:1.构建了B、C型S基因的氨基酸参考序列。2.B型突变率最高位点为200位点,C型为126位点。9个与疫苗逃避的重要突变位点中本文发现有5个,28个与隐匿性感染的位点中发现有17个。发现全基因中B型有氨基酸突变位点63个,C型有102个,两者比较差异有统计学意义(P0.05),两者共有氨基酸突变位点43个;"α"决定簇中B型有氨基酸突变位点8个,C型有10个,C型氨基酸突变位点数多于B型,但两者比较差异无统计学意义(P≥0.05),其中两者共有突变位点6个;B型与C型中"α"决定簇的氨基酸突变位点比例分别与全基因比较,差异均无统计学意义(P≥0.05)。全基因及"α"决定簇中C型发生突变的序列数比例远高于B型,差异均有统计学意义(P0.05);B和C型其"α"决定簇的氨基酸序列发生突变的序列数比例也远低于其全基因的氨基酸序列发生突变的序列数比例。全基因与"α"决定簇中C型氨基酸突变率均高于B型,差异有统计学意义(P0.05);C型"α"决定簇的氨基酸突变率高于其全基因的氨基酸突变率,两者比较差异有统计学意义(P0.05);B型"α"决定簇的氨基酸突变率高于其全基因的氨基酸突变率,但两者比较差异无统计学意义(P0.05)。3.C型S基因进化速率高于B型。Bayesian skyline plot显示B型S基因自1995年后遗传多样性不断降低,大约至2012年后趋于稳定;C型自1995年开始,遗传多样性逐渐增多,2000年以后遗传多样性达到高峰并趋于稳定,在2010年后,遗传多样性开始下降。4.B型ω值低于C型,两者均小于1。B型没有发现正向选择位点,发现8个负向选择位点;C型发现8个正向选择位点,17个负向选择位点。5.B型仅1个易突变位点:200位。C型也仅1个易突变位点:126位。研究结论:1.HBV S基因处于净化选择压力下。C型的氨基酸突变率高于B型,净化选择压力及保守性低于B型。2.C型自1995年开始遗传多样性经历一次扩张过程,B型遗传多样性处于降低趋势。3.C型经历免疫选择压力和自身净化压力双重影响,自身净化压力强于外界环境免疫选择压力;而B型主要遭受自身净化压力。
[Abstract]:Objective: to understand the evolutionary characteristics of HBV S gene and to provide a new theoretical basis for the cognition and prevention of hepatitis B. methods: NCBI "shanghai", "zhejiang" and "jiangsu" HBV S gene sequences were selected. The amino acid reference sequence of HBVS gene was constructed, and then the amino acid mutation of S gene was carried out. Analysis of selective pressure and amino acid replacement entropy. Results: 1. The amino acid reference sequence of the BU C S gene was constructed. The highest mutation rate of type B was 200 loci, and the highest mutation rate of C type was 126 loci. 9 of the 9 important mutation sites with vaccine escape were constructed. In this paper, we found that there were 5, 17 out of 28 occult infection sites, and 102 amino acid mutation sites of B type, 63 amino acid mutation sites in the whole gene. There were significant differences between the two groups (P 0.05), there were 43 amino acid mutation sites in the two groups, and 10 amino acid mutants in the "伪" determinant cluster with 8 amino acid mutation sites were more than those of B type, and the number of amino acid mutants of C type was more than that of B type in the "伪" determinant cluster. But there was no significant difference between the two groups (P 鈮，

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