轮状病毒VP7及NSP4蛋白适应性进化研究

发布时间：2018-03-25 18:19

本文选题：分子进化　切入点：最大似然法　出处：《南京航空航天大学》2009年硕士论文

【摘要】： 基因水平的适应性进化是一个遗传群体中以一种具有较高适合度的等位基因替代另一种等位基因的过程。检测某一物种的适应性进化有助于理解生物进化历史及相关结构与功能变异。轮状病毒是引起世界范围内人类和动物急性腹泻的传染病毒,其外壳蛋白VP7在诱导产生中和抗体中具有重要的作用,NSP4蛋白作为致泻蛋白,在疫苗研究中亦备受瞩目。目前对于轮状病毒的研究仅限于实验测序、基因分组、同源分析等方面。本研究旨在以统计学理论为依据,应用最大似然法方法(maximum likelihood,ML),对轮状病毒进行系统发育和适应性进化检测分析。对于特定地区及不同物种轮状病毒的进化模式及特点进行探讨分析。具体的研究内容及主要的创新之处如下: (1)以轮状病毒VP7、NSP4蛋白作为研究对象,以GenBank数据库为基础,从中筛选出中国区不同血清型完整序列,进行系统性的序列比对分析,并且构建了系统进化树,找出了中国区人轮状病毒不同血清型的轮状病毒VP7、NSP4蛋白编码序列异质性和变异规律。为中国区轮状病毒适应性进化分析提供了可靠的前提基础。 (2)利用最大似然法统计方法研究轮状病毒适应性进化,采用位点特异模型处理序列数据集,从分子层面找出中国地区人轮状病毒VP7和NSP4蛋白编码序列在进化过程中承受的正选择作用信号,发现了在NSP4蛋白序列中对于病毒功能分化及结构改变至关重要的位点信息。这也是本文研究的重要研究成果之一。本研究还将另一种适应性进化分析方法——Suzuki-Gojobori法应用于数据集,对两类方法试验结果进行比较分析。为今后中国地区轮状病毒疫苗的研制和流行病学检测提供了分子生物学依据。 (3)本研究还提出了不同物种轮状病毒VP7、NSP4的进化是否一致以及特定物种中如何进化的问题。通过自行筛选数据,选取不同物种VP7、NSP4蛋白编码序列为基础构建研究数据集。构建系统进化树,为后续研究绘制进化拓扑结构。通过分支模型,分支-位点模型的运用,识别了不同物种中轮状病毒VP7、NSP4不同的进化模式与特点。研究发现不同物种中的轮状病毒VP7、NSP4蛋白进化过程中占主导的为负选择作用,然而我们依旧在此背景下发现了特定物种中的正选择作用并识别出选择位点。找到了特定物种中的重要的免疫区域。本研究的结果不仅为人类轮状病毒,同时也为动物轮状病毒免疫提供了分子层面的依据,为轮状病毒漫长的分子研究进程做出了最初的探索。
[Abstract]:Adaptive evolution at the gene level is the process of replacing one allele with a higher fitness allele in a genetic population. Detecting the adaptive evolution of a species helps to understand the history of biological evolution and. Related structural and functional variations. Rotavirus is a virus that causes acute diarrhea in humans and animals worldwide. Its coat protein VP7 plays an important role in the production of neutralizing antibodies. At present, the research of rotavirus is limited to experimental sequencing, gene grouping, homology analysis and so on. The purpose of this study is to base on the statistical theory, The maximum likelihood method was used to detect and analyze the phylogenetic and adaptive evolution of rotavirus. The evolution patterns and characteristics of rotavirus in specific areas and different species were analyzed. And the main innovations are as follows:. 1) taking the rotavirus VP7nSP4 protein as the research object, based on GenBank database, the complete sequences of different serotypes in China were screened, and the systematic sequence alignment analysis was carried out, and the phylogenetic tree was constructed. The heterogeneity and variation of VP7NSP4 protein coding sequence of different serotypes of human rotavirus in China were found out, which provided a reliable basis for the adaptive evolution analysis of rotavirus in China. (2) the adaptive evolution of rotavirus was studied by maximum likelihood statistical method, and the sequence data set was processed by locus specific model. At the molecular level, the positive selection signals of the encoding sequences of human rotavirus VP7 and NSP4 proteins in China were identified in the course of evolution. The site information which is important to the differentiation and structural change of virus in NSP4 protein sequence is also one of the important research results in this paper. In this study, another adaptive evolutionary analysis method, Suzuki-Gojobori method, is also applied to the data set. The results of the two methods were compared and analyzed, which provided molecular biological basis for the development and epidemiological detection of rotavirus vaccine in China. (3) this study also raises the question of whether the evolution of rotavirus VP7NSP4 in different species is consistent and how it evolves in a particular species. Based on the coding sequence of VP7NSP4 protein from different species, we construct the phylogenetic tree and draw the evolutionary topology for further study. The application of branch model and branch-locus model is introduced. Different evolutionary patterns and characteristics of rotavirus VP7NSP4 in different species were identified. It was found that the dominant role in the evolution of rotavirus VP7NSP4 protein in different species was negative selection. In this context, however, we have found positive selection in specific species and identified selection sites. We have found important immune regions in specific species. The results of this study are not only human rotavirus, but also human rotavirus. It also provides molecular basis for animal rotavirus immunization, and makes initial exploration for the long molecular research process of rotavirus.
【学位授予单位】：南京航空航天大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R373

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