發(fā)布時間：2018-03-25 18:19

  本文選題：分子進化　切入點：最大似然法　出處：《南京航空航天大學》2009年碩士論文

【摘要】： 基因水平的適應性進化是一個遺傳群體中以一種具有較高適合度的等位基因替代另一種等位基因的過程。檢測某一物種的適應性進化有助于理解生物進化歷史及相關結構與功能變異。 輪狀病毒是引起世界范圍內人類和動物急性腹瀉的傳染病毒,其外殼蛋白VP7在誘導產(chǎn)生中和抗體中具有重要的作用,NSP4蛋白作為致瀉蛋白,在疫苗研究中亦備受矚目。目前對于輪狀病毒的研究僅限于實驗測序、基因分組、同源分析等方面。 本研究旨在以統(tǒng)計學理論為依據(jù),應用最大似然法方法(maximum likelihood,ML),對輪狀病毒進行系統(tǒng)發(fā)育和適應性進化檢測分析。對于特定地區(qū)及不同物種輪狀病毒的進化模式及特點進行探討分析。具體的研究內容及主要的創(chuàng)新之處如下: (1)以輪狀病毒VP7、NSP4蛋白作為研究對象,以GenBank數(shù)據(jù)庫為基礎,從中篩選出中國區(qū)不同血清型完整序列,進行系統(tǒng)性的序列比對分析,并且構建了系統(tǒng)進化樹,找出了中國區(qū)人輪狀病毒不同血清型的輪狀病毒VP7、NSP4蛋白編碼序列異質性和變異規(guī)律。為中國區(qū)輪狀病毒適應性進化分析提供了可靠的前提基礎。 (2)利用最大似然法統(tǒng)計方法研究輪狀病毒適應性進化,采用位點特異模型處理序列數(shù)據(jù)集,從分子層面找出中國地區(qū)人輪狀病毒VP7和NSP4蛋白編碼序列在進化過程中承受的正選擇作用信號,發(fā)現(xiàn)了在NSP4蛋白序列中對于病毒功能分化及結構改變至關重要的位點信息。這也是本文研究的重要研究成果之一。本研究還將另一種適應性進化分析方法——Suzuki-Gojobori法應用于數(shù)據(jù)集,對兩類方法試驗結果進行比較分析。為今后中國地區(qū)輪狀病毒疫苗的研制和流行病學檢測提供了分子生物學依據(jù)。 (3)本研究還提出了不同物種輪狀病毒VP7、NSP4的進化是否一致以及特定物種中如何進化的問題。通過自行篩選數(shù)據(jù),選取不同物種VP7、NSP4蛋白編碼序列為基礎構建研究數(shù)據(jù)集。構建系統(tǒng)進化樹,為后續(xù)研究繪制進化拓撲結構。通過分支模型,分支-位點模型的運用,識別了不同物種中輪狀病毒VP7、NSP4不同的進化模式與特點。研究發(fā)現(xiàn)不同物種中的輪狀病毒VP7、NSP4蛋白進化過程中占主導的為負選擇作用,然而我們依舊在此背景下發(fā)現(xiàn)了特定物種中的正選擇作用并識別出選擇位點。找到了特定物種中的重要的免疫區(qū)域。本研究的結果不僅為人類輪狀病毒,同時也為動物輪狀病毒免疫提供了分子層面的依據(jù),為輪狀病毒漫長的分子研究進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.
【學位授予單位】：南京航空航天大學
【學位級別】：碩士
【學位授予年份】：2009
【分類號】：R373

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