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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 selection pressure of S gene of B and C genotypes in Jiangsu, Zhejiang and Shanghai so as to provide a theoretical basis for the prevention and treatment of. Methods The hepatitis B virus sequences provided by the NCBI database were divided into two groups: B and C genotypes. Mutations were analyzed. Datamonkey was used for selective stress analysis and Bioedit for amino acid substitution entropy analysis. Results A total of 122 mutations were found in the 226 amino acid sequence of S gene. The mutation rate of C locus (45.58%) was higher than that of B genotype (30.09%) (χ ~ 2 = 11.523, P = 0.001 ). The overall mutation rate of C genotype (1.36%) was higher than that of B genotype (0.80%) (χ ~ 2 = 46.642, P = 0.000) (0.96%) (χ ~ 2 = 20.524, P = 0.000). The mutation rate of α determinant of B genotype was higher than the total mutation rate (χ ~ 2 = 0.735, P = 0.391). The mutation rate of α determinant of C genotype was higher than the total mutation rate (χ ~ 2 = 44.467, P = 0.000). The amino acid mutations of B genotype were the most frequently located at positions 200, 213, 161 and 21, while those with genotype C were 126,68, 3, 53 and 194. The mean dN / dS for both genotypes was less than 1. No positive selection site was found for the B genotype and 8 negative selection sites were found. C genotype found seven forward selection sites, 17 negative selection sites. Only one mutation site (200) was found in B genotype, only one mutation site was found in C genotype (126), and the entropy value of most amino acid sites was <0.4. Conclusions The mutation rate of S gene in Jiangsu, Zhejiang and Shanghai is lower. The mutation rate of C genotype, the mutation rate of α determinant and the total mutation rate are higher than that of B genotype. The mutation rate of α determinant is higher than the total mutation rate. C genotypes under the dual influence of external environment immune selection pressure and self-evolutionary pressure, self-evolutionary pressure is stronger than external environment immune selection pressure; and genotype B mainly suffers from its own evolutionary pressure. In particular, pay special attention to the evolution of C genotypes.