本文選題：分子進(jìn)化　切入點(diǎn)：最大似然法　出處：《南京航空航天大學(xué)》2009年碩士論文

【摘要】： 基因水平的適應(yīng)性進(jìn)化是一個(gè)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(guò)程。檢測(cè)某一物種的適應(yīng)性進(jìn)化有助于理解生物進(jìn)化歷史及相關(guān)結(jié)構(gòu)與功能變異。 輪狀病毒是引起世界范圍內(nèi)人類和動(dòng)物急性腹瀉的傳染病毒,其外殼蛋白VP7在誘導(dǎo)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(duì)于輪狀病毒的研究?jī)H限于實(shí)驗(yàn)測(cè)序、基因分組、同源分析等方面。 本研究旨在以統(tǒng)計(jì)學(xué)理論為依據(jù),應(yīng)用最大似然法方法(maximum likelihood,ML),對(duì)輪狀病毒進(jìn)行系統(tǒng)發(fā)育和適應(yīng)性進(jìn)化檢測(cè)分析。對(duì)于特定地區(qū)及不同物種輪狀病毒的進(jìn)化模式及特點(diǎn)進(jìn)行探討分析。具體的研究?jī)?nèi)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(duì)象,以GenBank數(shù)據(jù)庫(kù)為基礎(chǔ),從中篩選出中國(guó)區(qū)不同血清型完整序列,進(jìn)行系統(tǒng)性的序列比對(duì)分析,并且構(gòu)建了系統(tǒng)進(jìn)化樹(shù),找出了中國(guó)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(zhì)性和變異規(guī)律。為中國(guó)區(qū)輪狀病毒適應(yīng)性進(jìn)化分析提供了可靠的前提基礎(chǔ)。 (2)利用最大似然法統(tǒng)計(jì)方法研究輪狀病毒適應(yīng)性進(jìn)化,采用位點(diǎn)特異模型處理序列數(shù)據(jù)集,從分子層面找出中國(guó)地區(qū)人輪狀病毒VP7和NSP4蛋白編碼序列在進(jìn)化過(guò)程中承受的正選擇作用信號(hào),發(fā)現(xiàn)了在NSP4蛋白序列中對(duì)于病毒功能分化及結(jié)構(gòu)改變至關(guān)重要的位點(diǎn)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(yīng)性進(jìn)化分析方法——Suzuki-Gojobori法應(yīng)用于數(shù)據(jù)集,對(duì)兩類方法試驗(yàn)結(jié)果進(jìn)行比較分析。為今后中國(guó)地區(qū)輪狀病毒疫苗的研制和流行病學(xué)檢測(cè)提供了分子生物學(xué)依據(jù)。 (3)本研究還提出了不同物種輪狀病毒VP7、NSP4的進(jìn)化是否一致以及特定物種中如何進(jìn)化的問(wèn)題。通過(guò)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(chǔ)構(gòu)建研究數(shù)據(jù)集。構(gòu)建系統(tǒng)進(jìn)化樹(shù),為后續(xù)研究繪制進(jìn)化拓?fù)浣Y(jié)構(gòu)。通過(guò)分支模型,分支-位點(diǎn)模型的運(yùn)用,識(shí)別了不同物種中輪狀病毒VP7、NSP4不同的進(jìn)化模式與特點(diǎn)。研究發(fā)現(xiàn)不同物種中的輪狀病毒VP7、NSP4蛋白進(jìn)化過(guò)程中占主導(dǎo)的為負(fù)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(shí)別出選擇位點(diǎn)。找到了特定物種中的重要的免疫區(qū)域。本研究的結(jié)果不僅為人類輪狀病毒,同時(shí)也為動(dòng)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(zhǎng)的分子研究進(jìn)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(xué)位授予單位】：南京航空航天大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2009
【分類號(hào)】：R373

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 杜德偉,周永興,白憲光,馮志華,李光玉,姚志強(qiáng);小鼠對(duì)HBV DNA疫苗的免疫應(yīng)答及細(xì)胞因子的免疫佐劑效應(yīng)[J];醫(yī)學(xué)研究生學(xué)報(bào);2001年02期

2 金輝,王蓓,汪寧;A組輪狀病毒的分子流行病學(xué)研究進(jìn)展[J];江蘇預(yù)防醫(yī)學(xué);2003年01期

3 張?jiān)?鄭楠,郝沛,鐘揚(yáng);SARS冠狀病毒S基因的最近共同祖先序列重建及Spike蛋白的適應(yīng)性進(jìn)化檢測(cè)[J];科學(xué)通報(bào);2004年11期

4 張文娟;張?jiān)?鐘揚(yáng);;應(yīng)用最大似然法檢測(cè)丙肝病毒包膜蛋白編碼基因的適應(yīng)性進(jìn)化[J];科學(xué)通報(bào);2006年16期

5 白植生,陳冬梅,申碩;口服輪狀病毒活疫苗LLR-85株的選育及鑒定[J];中國(guó)生物制品學(xué)雜志;1994年02期

6 呂雪萍,劉建軍,張留英,袁煥珍;輪狀病毒多系統(tǒng)感染的診斷及治療[J];實(shí)用兒科臨床雜志;2003年11期

7 任文華,崔志洪;豬輪狀病毒概述[J];畜牧獸醫(yī)雜志;2005年05期

8 陳劍杰;李巨銀;;禽輪狀病毒研究進(jìn)展[J];畜牧獸醫(yī)雜志;2007年01期

9 王大燕;王健偉;于修平;洪濤;;輪狀病毒致病機(jī)制研究進(jìn)展[J];世界華人消化雜志;2003年11期

10 唐麗杰,師東方,李一經(jīng),王榮軍;豬傳染性胃腸炎病毒核衣殼N蛋白基因的克隆與鑒定[J];中國(guó)獸醫(yī)科技;2002年01期

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