本文關(guān)鍵詞： GII.4諾如病毒 共發(fā)生網(wǎng)絡(luò) 基因組 進(jìn)化　出處：《南華大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：利用生物信息學(xué)方法建立GII.4型諾如病毒的進(jìn)化模型，探討1974年至2010年世界范圍GII.4諾如病毒的進(jìn)化機(jī)制和動(dòng)力學(xué)規(guī)律，找出影響GII.4諾如病毒進(jìn)化的重要氨基酸位點(diǎn)，為預(yù)防和控制諾如病毒胃腸炎的暴發(fā)流行提供基礎(chǔ)數(shù)據(jù)。 方法：通過構(gòu)建核苷酸共發(fā)生網(wǎng)絡(luò)（Co-occurrence Network）來分析GII.4型諾如病毒進(jìn)化的潛在模式。利用軟件Muscle比對(duì)233條1974年至2010年來自9個(gè)國(guó)家的GII.4諾如病毒全基因組序列；去除其中的保守核苷酸位點(diǎn)，從不保守位點(diǎn)中提取出呈現(xiàn)完美共發(fā)生現(xiàn)象的核苷酸對(duì)，連接所有的完美共發(fā)生核苷酸對(duì)，，利用軟件Cytoscape顯示共發(fā)生網(wǎng)絡(luò)并計(jì)算網(wǎng)絡(luò)拓?fù)涮卣鳎贿M(jìn)一步編程將網(wǎng)絡(luò)中的核苷酸對(duì)聚類成共發(fā)生核苷酸模塊，使用軟件Expander分析每一個(gè)共發(fā)生核苷酸模塊并從中提取出能揭示病毒的生物學(xué)活性的具有協(xié)同作用的共變異核苷酸。 結(jié)果： 1. GII.4諾如病毒基因組核苷酸替代分析發(fā)現(xiàn)病毒核苷酸序列變異數(shù)隨著時(shí)間不斷增加，表明諾如病毒的進(jìn)化是隨時(shí)間蓄積的。 2.共發(fā)生網(wǎng)絡(luò)連接度分析表明GII.4諾如病毒網(wǎng)絡(luò)連接度的變化可以定量地反映病毒抗原性的變化，當(dāng)網(wǎng)絡(luò)連接度在某一季節(jié)出現(xiàn)了變化高峰時(shí)，意味著新的病毒變異株的出現(xiàn)及疫情暴發(fā)的可能；網(wǎng)絡(luò)連接度的分析結(jié)果與傳統(tǒng)的系統(tǒng)進(jìn)化分析結(jié)果一致。 3.基因片段的分析顯示在GII.4諾如病毒進(jìn)化過程中，基因組內(nèi)的各個(gè)基因片段都起著相應(yīng)的推動(dòng)作用，即病毒的進(jìn)化是全基因組水平上的共進(jìn)化。 4.通過對(duì)共發(fā)生核苷酸模塊的分析，找到了諾如病毒基因組的各個(gè)基因片段中對(duì)于病毒進(jìn)化起關(guān)鍵作用的相應(yīng)氨基酸位點(diǎn)。 結(jié)論： 1.核苷酸共發(fā)生網(wǎng)絡(luò)模型是分析病毒進(jìn)化的一種既簡(jiǎn)單又準(zhǔn)確的方法，它可以作為傳統(tǒng)系統(tǒng)進(jìn)化分析方法的一個(gè)補(bǔ)充，并可以對(duì)諾如病毒疫情的暴發(fā)提供有效的預(yù)警。 2. GII.4病毒的進(jìn)化是基因組水平上的共進(jìn)化。 3.基因組中與病毒受體結(jié)合部位表現(xiàn)出共進(jìn)化關(guān)系的氨基酸位點(diǎn)對(duì)病毒的進(jìn)化作用可能更大，仍需定點(diǎn)突變實(shí)驗(yàn)證實(shí)。
[Abstract]:Objective: to establish an evolutionary model of GII.4 type norovirus by bioinformatics, and to explore the evolutionary mechanism and kinetics of GII.4 norovirus from 1974 to 2010, and to find out the important amino acid sites that affect the evolution of GII.4 norovirus. Provide basic data to prevent and control the outbreak of norovirus gastroenteritis. Methods: to analyze the potential model of GII.4 type Norovirus evolution by constructing co-occurrence network of nucleotide co-occurrence network. The whole genome sequence of GII.4 Norovirus from 1974 to 2010 was compared with the software Muscle. Removing the conserved nucleotide sites and extracting the perfect co-occurrence nucleotide pairs from the unconserved sites, connecting all the perfect co-occurrence nucleotide pairs, using the software Cytoscape to display the co-occurrence network and calculate the network topology characteristics; Further programming the nucleotide pairs in the network to cluster into co-nucleotide modules and using software Expander to analyze each co-nucleotide module and extract covariant nucleotides with synergistic effect which can reveal the biological activity of the virus. Results:. 1. Nucleotide substitution analysis of GII.4 norovirus genome showed that the variation of nucleotide sequence increased with time, indicating that the evolution of norovirus accumulated over time. 2. The analysis of cooccurrence network connectivity shows that the change of network connectivity of GII.4 Norovirus can reflect the change of virus antigenicity quantitatively, and when the network connectivity reaches its peak in a certain season, This means the emergence of new virus variants and the possibility of outbreak. The results of network connectivity analysis are consistent with the results of traditional phylogenetic analysis. 3. The analysis of gene fragments shows that in the evolution of GII.4 Norovirus, each gene fragment in the genome plays a corresponding role, that is, the evolution of the virus is coevolution at the whole genome level. 4. Based on the analysis of cooccurrence nucleotide modules, the corresponding amino acid sites which play a key role in the evolution of Noroviruses were found in each gene fragment of Norovirus genome. Conclusion:. 1. The nucleotide cooccurrence network model is a simple and accurate method to analyze virus evolution. It can be used as a supplement to the traditional phylogenetic analysis method and can provide an effective early warning for the outbreak of Norovirus. 2. The evolution of GII.4 virus is coevolution at genome level. 3. The coevolution of amino acid sites in genomes with coevolutionary relationship with viral receptor sites may be more important for virus evolution, which still needs to be confirmed by site-directed mutation experiments.
【學(xué)位授予單位】：南華大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R373

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