中国地区H3N2亚型人流感病毒NS1基因分子进化研究

发布时间：2018-05-17 04:33

本文选题：甲型流感病毒 + H3N2／NS1基因　；参考：《湖南师范大学》2009年硕士论文

【摘要】： 甲型H3N2流感病毒是威胁人类健康的重要病原体之一,中国地区是世界上流感变异株策源地之一,NS1基因是流感病毒主要的毒力因子之一,对其变异规律进行深入的分析研究在流感的防治工作中具有重要的参考意义。本研究借助近年来发展起来的初步的数据挖掘技术和进化树分析方法,从生物信息学的角度对流感病毒H3N2/NS1基因的变异规律进行了系统研究,主要包括以下内容: 1、聚类分析对序列的变异规律进行初步分析应用两步聚类法进行了NS1序列的类别分析,结果显示全部H3N2/NS1序列可以被清楚的分为4类,各类在宿主间的分布特征清楚的反映了不同宿主序列间亲缘关系的远近,而时间分布上则反映了H3N2/NS1基因在人群中不断传播和变异的过程。 2、序列的进化树分析分析结果显示,进化树结构和聚类结果基本一致,相应结果不仅详细刻画了数十年来H3N2流感病毒NS1基因变异的基本规律,还解释了两个关键问题:猪宿主在人流感病毒变异中起基因混合器的作用;与全球其余地区相比,中国南部地区在人H3N2亚型流感病毒的NS1变异中显示出早期策源地,但并不是后期主要的变异株起源地。 3、正向选择位点鉴定运用正向选择模型分析了所有H3N2/NS1序列信息。结果表明,人流感病毒H3N2/NS1基因所承受的选择压力是逐渐增大的,并且在90年代年后期达到高峰。在被筛选出的10个正向位点中,绝大多数都具有适应性进化的重要意义。本研究在回答流行病学问题的同时,还试探性地建立遗传序列变异规律研究的方法体系,分析结果显示,这一系列方法能够很好的满足分子流行病学中相应分析的需求,值得进一步改进和应用。
[Abstract]:Influenza A (H3N2) virus is one of the most important pathogens threatening human health. The NS1 gene is one of the major virulence factors of influenza virus in China. It is of great significance to analyze and study the variation of influenza in the prevention and treatment of influenza. With the help of the preliminary data mining technology and evolutionary tree analysis method developed in recent years, the variation of H3N2/NS1 gene of influenza virus was systematically studied from the perspective of bioinformatics, including the following contents: 1. Cluster analysis was used to analyze the variation rule of sequence. A two-step clustering method was used to analyze the NS1 sequences. The results showed that all H3N2/NS1 sequences could be clearly classified into four categories, and the distribution characteristics among hosts clearly reflected the distance and proximity of the genetic relationships between different host sequences. The time distribution reflects the continuous transmission and variation of H3N2/NS1 gene in the population. 2. Evolutionary tree analysis of sequences The results show that the evolutionary tree structure is basically consistent with the clustering results, and the corresponding results not only describe the basic rules of NS1 gene variation of H3N2 influenza virus in recent decades. It also explains two key issues: the role of pig hosts as a gene mixer in human influenza virus mutations, and the early origin of human H3N2 subtype NS1 mutations in southern China compared with the rest of the world. But it is not the origin of the main mutant in the later stage. 3, positive selection site identification The forward selection model is used to analyze all H3N2/NS1 sequence information. The results showed that the selection pressure of H3N2/NS1 gene of human influenza virus increased gradually and reached its peak in the late 1990s. Most of the 10 positive loci screened have the significance of adaptive evolution. While answering the epidemiological questions, this study also tentatively established a method system for the study of the law of genetic sequence variation. The results showed that this series of methods could well meet the needs of the corresponding analysis in molecular epidemiology. It is worthy of further improvement and application.
【学位授予单位】：湖南师范大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R373

【共引文献】