發(fā)布時(shí)間：2018-05-16 07:24

  本文選題：病原微生物 + 比較基因組學(xué)��； 參考：《中國(guó)科學(xué)院研究生院（上海生命科學(xué)研究院）》2007年博士論文

【摘要】： 由病原微生物引起的感染,特別是爆發(fā)性的疾病,一直是人類(lèi)健康的主要威脅之一。隨著基因組學(xué)的發(fā)展,越來(lái)越多的全基因組序列被測(cè)序研究。對(duì)基因組序列進(jìn)行比較分析,并探索基因組序列結(jié)構(gòu)與病原微生物的致病能力的關(guān)系的比較基因組學(xué)也應(yīng)運(yùn)而生,對(duì)病原微生物學(xué)的研究注入了新的活力。 基于我們自己發(fā)展的比較基因組生物信息學(xué)分析方法和策略,我們對(duì)多種病原微生物的基因組序列進(jìn)行了比較分析。包括能夠?qū)е氯诵蟾腥镜呢i鏈球菌,能引起伴隨外源植入的醫(yī)療設(shè)備感染的表皮葡萄球菌,還有從感染肺炎的艾滋病病人分離得到的釀酒酵母YJM789菌株。 在對(duì)豬鏈球菌的研究中,我們首次對(duì)已測(cè)序的豬鏈球菌(Streptococcus suis)的兩個(gè)菌株(P1/7, 89-1591)進(jìn)行了全面的功能注釋和分析比較。比較結(jié)果顯示兩個(gè)基因組有1306個(gè)同源基因,兩菌株中可能的毒性因子大多數(shù)具同源性,4個(gè)莢膜多糖基因cps2A,2B,2I,2J只在P1/7菌株中發(fā)現(xiàn)。另外還第一次在P1/7菌株中鑒定到了8個(gè)可能與其致病性相關(guān)的基因島。 在表皮葡萄球菌基因組序列分析研究中,通過(guò)對(duì)ATCC1228菌株和RP62A菌株之間的SNP序列通過(guò)dN/dS的值差異的統(tǒng)計(jì)學(xué)分析找到了的40個(gè)可能與致病性相關(guān)的基因。生物學(xué)功能分析發(fā)現(xiàn),這些基因可分為兩類(lèi),一類(lèi)是可能會(huì)在逃避免疫系統(tǒng)中起作用的表面蛋白;另一類(lèi)是對(duì)在新的環(huán)境中生存非常重要的基因。研究發(fā)現(xiàn)其中的甲硫氨酸亞砜還原酶可能會(huì)在凈化活性氧過(guò)程中起作用,隨后,我們對(duì)兩株細(xì)菌進(jìn)行了在有氧化劑存在的條件下的生存能力的試驗(yàn),試驗(yàn)結(jié)果也證實(shí)了兩株菌在抗氧化生存能力上的差異。 在對(duì)表皮葡萄球菌和釀酒酵母YJM789菌株的基因組序列分析研究中,我們進(jìn)行了YJM789的全基因組序列與試驗(yàn)菌株S288c的比較分析,表明兩者的基因組之間有59000個(gè)SNPs(單核苷酸多態(tài)性),和約45Kb的插入缺失。兩者在1號(hào)染色體的右臂有一段區(qū)域的多態(tài)性的差異顯著的大于其他區(qū)域,其中包括5個(gè)膜蛋白,分析顯示其可能來(lái)自于進(jìn)化上與酵母Saccharomyces paradoxus相近的真菌的基因滲入。而編碼多藥抗性的基因PDR5,也表現(xiàn)出了與周?chē)鷧^(qū)域差異顯著的高多態(tài)性。另外還發(fā)現(xiàn)包括GCN5相關(guān)的N-乙�；D(zhuǎn)移酶和糖蜜抗性蛋白在內(nèi)的幾個(gè)蛋白是從其它的微生物平行轉(zhuǎn)移而來(lái)。 我們對(duì)以上病原微生物物種內(nèi)的單核苷酸多態(tài)序列,插入缺失等這些序列多態(tài),與致病能力的相關(guān)性進(jìn)行了仔細(xì)深入的研究。我們的研究為病原微生物的毒性因子的鑒定提供了新的方法,為病原微生物的致病機(jī)制的理解提供了新的思路。同時(shí)也為以上重要病原微生物的致病機(jī)理的分子機(jī)制的研究以及防治、疫苗的開(kāi)發(fā)、治療藥物的設(shè)計(jì)等提供了廣泛的基因組學(xué)信息。
[Abstract]:Infection caused by pathogenic microorganisms, especially the explosive disease, has been one of the major threats to human health. With the development of genomics, more and more genome sequences have been sequenced. The comparative analysis of genome sequences and the comparison of the relationship between the genome sequence and the pathogenicity of the pathogenic microorganism Comparative genomics has also emerged, which has injected new vitality into the research of pathogenic microbiology.
Based on our own developed comparative genomic bioinformatics analysis methods and strategies, we compare the genome sequences of various pathogenic microorganisms, including Streptococcus suis, which can lead to human and animal infections, which can cause Staphylococcus epidermidis infected with medical equipment with exogenous implantation, and AIDS infected with pneumonia. The isolated strain of Saccharomyces cerevisiae YJM789 was isolated from the patient.
In the study of Streptococcus suis, we made a comprehensive functional annotation and analysis of two strains of Streptococcus suis (Streptococcus suis) (P1/7, 89-1591), which had been sequenced for the first time. The results showed that two genomes had 1306 homologous genes, and the most likely toxicity factors of the two strains were homologous, 4 capsular polysaccharide genes were found. Cps2A, 2B, 2I and 2J were found only in P1/7 strain. In addition, the 8 gene islands related to pathogenicity were identified in P1/7 strain for the first time.
In the genome sequence analysis of Staphylococcus epidermidis, 40 genes related to pathogenicity were found by statistical analysis of the difference between the SNP sequence of the ATCC1228 strain and the RP62A strain through the difference in the value of dN/dS. The biological functional analysis found that these genes could be divided into two categories, one of which might be in the escape of the immune system. The effect of surface proteins; the other is a very important gene for the survival of the new environment. The study found that the methionine sulfoxide reductase may play a role in the purification of reactive oxygen species. Then, we have tested the viability of two strains of bacteria under the presence of oxidants, and the results have also been confirmed. The difference in antioxidant viability between two strains of bacteria.
In the genomic sequence analysis of Staphylococcus epidermidis and Saccharomyces cerevisiae strain YJM789, we compared the whole genome sequence of YJM789 with the test strain S288c, which showed that there were 59000 SNPs (single nucleotide polymorphisms) between the two genomes and the insertion deletion of about 45Kb. Both of them had a section on the right arm of chromosome 1. The polymorphism of the region was significantly greater than that in other regions, including 5 membrane proteins. Analysis showed that it might come from the genetic infiltration of the fungi that were similar to the yeast Saccharomyces paradoxus. The gene PDR5 encoding the multidrug resistance also showed high polymorphism in the surrounding region. In addition, it was found to include GC N5 related N- acetyltransferases and molasses resistant proteins are parallel transferred from other microorganisms.
We studied the polymorphism of single nucleotide polymorphisms in the pathogenic microorganism species, insertion deletion and so on, and studied the correlation with the pathogenicity. Our study provides a new method for the identification of the toxic factors of pathogenic microbes and provides a new idea for the understanding of pathogenic mechanism of pathogenic microbes. It also provides a wide range of genomics information for the molecular mechanism of the pathogenic mechanism of the important pathogenic microbes, the prevention and control of the vaccine, the development of the vaccine, and the design of the therapeutic drugs.

【學(xué)位授予單位】：中國(guó)科學(xué)院研究生院（上海生命科學(xué)研究院）
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2007
【分類(lèi)號(hào)】：R37

【引證文獻(xiàn)】

相關(guān)博士學(xué)位論文 前1條

1 李貴陽(yáng);兩株鰻弧菌全基因組序列測(cè)定及轉(zhuǎn)錄組比較分析[D];中國(guó)科學(xué)院研究生院（海洋研究所）;2011年

相關(guān)碩士學(xué)位論文 前1條

1 季舒涵;牛A-FABP多克隆抗血清制備及組織表達(dá)分析[D];西北農(nóng)林科技大學(xué);2010年

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本文編號(hào)：1895979