本文關(guān)鍵詞： HBV S 基因 突變率 進(jìn)化 選擇壓力 氨基酸置換熵值　出處：《浙江大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：研究目的:了解HBV S基因進(jìn)化特征情況,為乙型肝炎的認(rèn)知和防治提供新的理論依據(jù)。研究方法:選取 NCBI"shanghai"、"zhejiang"、"jiangsu"三地 HBV S 基因序列,共 375 條,分成B和C型兩組。首先構(gòu)建HBVS基因的氨基酸參考序列,然后進(jìn)行S基因的氨基酸突變情況、遺傳多樣性動(dòng)態(tài)變化、選擇壓力及氨基酸置換熵值分析。研究結(jié)果:1.構(gòu)建了B、C型S基因的氨基酸參考序列。2.B型突變率最高位點(diǎn)為200位點(diǎn),C型為126位點(diǎn)。9個(gè)與疫苗逃避的重要突變位點(diǎn)中本文發(fā)現(xiàn)有5個(gè),28個(gè)與隱匿性感染的位點(diǎn)中發(fā)現(xiàn)有17個(gè)。發(fā)現(xiàn)全基因中B型有氨基酸突變位點(diǎn)63個(gè),C型有102個(gè),兩者比較差異有統(tǒng)計(jì)學(xué)意義(P0.05),兩者共有氨基酸突變位點(diǎn)43個(gè);"α"決定簇中B型有氨基酸突變位點(diǎn)8個(gè),C型有10個(gè),C型氨基酸突變位點(diǎn)數(shù)多于B型,但兩者比較差異無統(tǒng)計(jì)學(xué)意義(P≥0.05),其中兩者共有突變位點(diǎn)6個(gè);B型與C型中"α"決定簇的氨基酸突變位點(diǎn)比例分別與全基因比較,差異均無統(tǒng)計(jì)學(xué)意義(P≥0.05)。全基因及"α"決定簇中C型發(fā)生突變的序列數(shù)比例遠(yuǎn)高于B型,差異均有統(tǒng)計(jì)學(xué)意義(P0.05);B和C型其"α"決定簇的氨基酸序列發(fā)生突變的序列數(shù)比例也遠(yuǎn)低于其全基因的氨基酸序列發(fā)生突變的序列數(shù)比例。全基因與"α"決定簇中C型氨基酸突變率均高于B型,差異有統(tǒng)計(jì)學(xué)意義(P0.05);C型"α"決定簇的氨基酸突變率高于其全基因的氨基酸突變率,兩者比較差異有統(tǒng)計(jì)學(xué)意義(P0.05);B型"α"決定簇的氨基酸突變率高于其全基因的氨基酸突變率,但兩者比較差異無統(tǒng)計(jì)學(xué)意義(P0.05)。3.C型S基因進(jìn)化速率高于B型。Bayesian skyline plot顯示B型S基因自1995年后遺傳多樣性不斷降低,大約至2012年后趨于穩(wěn)定;C型自1995年開始,遺傳多樣性逐漸增多,2000年以后遺傳多樣性達(dá)到高峰并趨于穩(wěn)定,在2010年后,遺傳多樣性開始下降。4.B型ω值低于C型,兩者均小于1。B型沒有發(fā)現(xiàn)正向選擇位點(diǎn),發(fā)現(xiàn)8個(gè)負(fù)向選擇位點(diǎn);C型發(fā)現(xiàn)8個(gè)正向選擇位點(diǎn),17個(gè)負(fù)向選擇位點(diǎn)。5.B型僅1個(gè)易突變位點(diǎn):200位。C型也僅1個(gè)易突變位點(diǎn):126位。研究結(jié)論:1.HBV S基因處于凈化選擇壓力下。C型的氨基酸突變率高于B型,凈化選擇壓力及保守性低于B型。2.C型自1995年開始遺傳多樣性經(jīng)歷一次擴(kuò)張過程,B型遺傳多樣性處于降低趨勢。3.C型經(jīng)歷免疫選擇壓力和自身凈化壓力雙重影響,自身凈化壓力強(qiáng)于外界環(huán)境免疫選擇壓力;而B型主要遭受自身凈化壓力。
[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 "偽" 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 "偽" determinant cluster. But there was no significant difference between the two groups (P 鈮，

本文編號(hào)：1550049