【摘要】：選擇性剪接事件是真核生物的一種基本而重要的調(diào)控機(jī)制。通過不同的剪接方式,剪接獲得的基因序列可以組合產(chǎn)生多種不同的mRNA剪接異構(gòu)體。這些mRNA剪接異構(gòu)體被翻譯成不同結(jié)構(gòu)的蛋白產(chǎn)物或是功能相互拮抗的蛋白產(chǎn)物。鑒于表達(dá)水平的不同,在同一細(xì)胞中產(chǎn)生不同的表型。選擇性剪接事件的發(fā)生為僅擁有20000～25000個(gè)基因的人類執(zhí)行了復(fù)雜的生理功能,因此,對(duì)選擇性剪接事件的研究有助于揭示人類機(jī)體的功能機(jī)制,認(rèn)識(shí)人類生命的本質(zhì)。基因承載著決定生物性狀的遺傳信息,蛋白質(zhì)是生物機(jī)體內(nèi)功能的執(zhí)行者�；蛐蛄袥Q定蛋白質(zhì)的氨基酸序列,蛋白質(zhì)的氨基酸序列決定蛋白質(zhì)的結(jié)構(gòu),蛋白質(zhì)的結(jié)構(gòu)狀態(tài)決定蛋白質(zhì)的功能。由此可見,基因與蛋白質(zhì)的結(jié)構(gòu)和功能之間具有一脈相承的關(guān)系�；蛐蛄械淖兓瘜⒂绊懼鞍踪|(zhì)的序列組成,進(jìn)而影響著蛋白質(zhì)的結(jié)構(gòu)和功能。選擇性剪接事件的發(fā)生能夠改變基因序列,也就意味著會(huì)對(duì)蛋白質(zhì)的結(jié)構(gòu)和功能產(chǎn)生重要的影響。從這個(gè)角度出發(fā),本課題著重分析選擇性剪接事件對(duì)基因功能以及產(chǎn)物蛋白結(jié)構(gòu)的影響。具體從以下四個(gè)方面進(jìn)行研究:(1)鑒于選擇性剪接事件發(fā)生的不確定性,分析選擇性剪接事件發(fā)生的有效性。首先,在MISO數(shù)據(jù)庫(kù)中獲取所有的選擇性剪接事件數(shù)據(jù),鑒于選擇性剪接事件的不確定性,根據(jù)判斷選擇性剪接事件數(shù)據(jù)有效性的規(guī)則,對(duì)選擇性剪接事件數(shù)據(jù)進(jìn)行分析與處理,最后,提取所有符合判別規(guī)則的選擇性剪接事件數(shù)據(jù),并用做本文后續(xù)研究的實(shí)驗(yàn)數(shù)據(jù)。(2)分析發(fā)生選擇性剪接事件的基因功能。首先,根據(jù)選擇性剪接事件注釋信息獲取基因序列的信息,依據(jù)選擇性剪接事件對(duì)基因編碼子的影響程度,將選擇性剪接事件劃分為兩類:改變?cè)芯幋a框的選擇性剪接事件Ⅰ類和保留原有編碼框的選擇性剪接事件Ⅱ類,然后利用GO,對(duì)發(fā)生選擇性剪接事件的基因進(jìn)行功能分析,分析兩類剪事件中基因的功能類別。分析結(jié)果表明,兩類剪接事件具有最多的基因功能是酶的催化作用,其次是連接功能,最少的是通路調(diào)控。此外,對(duì)比改變和保留原有編碼框的選擇性剪接事件發(fā)現(xiàn)基因功能并沒有明顯差異。(3)構(gòu)建選擇性剪接事件中基因序列到氨基酸序列的翻譯模型。三個(gè)核苷酸能夠編碼一個(gè)氨基酸,基因與蛋白質(zhì)之間存在著生物密碼子表。本文首先分析現(xiàn)有翻譯軟件在翻譯選擇性剪接事件的基因序列中存在的問題,然后針對(duì)選擇性剪接事件的特點(diǎn),提出基因序列翻譯成氨基酸序列的規(guī)則,最后根據(jù)翻譯規(guī)則,將選擇性剪接事件中基因序列翻譯成氨基酸序列。從翻譯模型得出的結(jié)果,共翻譯出39541條氨基酸序列。(4)分析選擇性剪接事件對(duì)其產(chǎn)物蛋白結(jié)構(gòu)的影響。本文利用VSL2無序蛋白結(jié)構(gòu)預(yù)測(cè)模型,預(yù)測(cè)選擇性剪接事件中蛋白產(chǎn)物的無序結(jié)構(gòu),同時(shí)也預(yù)測(cè)了無序區(qū)域的長(zhǎng)度。預(yù)測(cè)結(jié)果顯示,選擇性剪接會(huì)使產(chǎn)物蛋白具有無序結(jié)構(gòu)的傾向性。
[Abstract]:Alternative splicing events are a basic and important regulatory mechanism of eukaryotes. By different splicing methods, the gene sequences obtained by splicing can be combined to produce a variety of different mRNA splice isoforms. These mRNA splice isoforms are translated into protein products of different structures or functionally antagonistic protein products. In view of the differences in the level of expression, different phenotypes are produced in the same cell. The occurrence of alternative splicing events is a complex physiological function for humans with only 20000-25000 genes, so the study of alternative splicing events can help to reveal the human body's functional mechanism and recognize the nature of human life. The gene carries the genetic information that determines the biological character, and the protein is the performer of the function in the biological body. The gene sequence determines the amino acid sequence of the protein, the amino acid sequence of the protein determines the structure of the protein, the structural state of the protein determines the function of the protein. Thus, there is a relationship between the structure and function of the gene and the protein. The change of the gene sequence will affect the sequence composition of the protein, thus affecting the structure and function of the protein. The occurrence of a selective splicing event can change the sequence of genes, which means an important effect on the structure and function of the protein. From this point of view, this subject focuses on the analysis of the effects of alternative splicing events on gene function and product protein structure. The study was carried out in the following four aspects: (1) the effectiveness of the selective splicing event was analyzed in view of the uncertainty of the selective splicing event. first, all the alternative splicing event data is obtained in the MISO database, and in view of the uncertainty of the selective splicing event, the selective splicing event data is analyzed and processed according to the rules for judging the validity of the selective splicing event data, and finally, All the alternative splicing event data in accordance with the criteria for discrimination were extracted and the experimental data for subsequent studies in this paper were used. (2) The gene function of the selective splicing event was analyzed. first, according to the information of the selective splicing event annotation information to obtain the gene sequence, the selective splicing event is divided into two types according to the degree of the effect of the selective splicing event on the gene coding sub-; The selective splicing event type I of the original coding frame and the selective splicing event type II of the original coding frame are changed, and then the function of the gene in the two types of scissors events is analyzed by using the GO and the function analysis of the gene which has the selective splicing event. The results of the analysis show that the two types of splicing events have the most gene function as the catalytic action of the enzyme, the second is the connection function, and the least is the pathway regulation. In addition, there was no significant difference in the gene function compared to the alternative splicing events that alter and retain the original coding frame. (3) constructing a translation model of a gene sequence in a selective splicing event to an amino acid sequence. The three nucleonic acid can encode an amino acid, and there is a biological codon table between the gene and the protein. In this paper, the problems of the existing translation software in the translation of alternative splicing events are analyzed, and then the rules for the translation of the gene sequence into the amino acid sequence are put forward according to the characteristics of the selective splicing event, and finally, according to the translation rule, The gene sequence in a selective splicing event is translated into an amino acid sequence. A total of 39541 amino acid sequences were translated from the results of the translation model. (4) The effect of alternative splicing events on its product protein structure was analyzed. In this paper, the unordered structure of the protein product in the selective splicing event is predicted by using the VSL2 disorder protein structure prediction model, and the length of the disorder region is also predicted. The results of the prediction show that alternative splicing can lead to the tendency of the product protein to have a disordered structure.
【學(xué)位授予單位】：哈爾濱工程大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：Q78

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本文編號(hào)：2501756