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川桑密碼子使用模式與密碼子分析工具的開(kāi)發(fā)

發(fā)布時(shí)間:2018-08-06 11:23
【摘要】:密碼子是m RNA上的三個(gè)連續(xù)核苷酸,是合成蛋白質(zhì)時(shí)核苷酸編碼氨基酸的規(guī)律。遺傳密碼的破譯對(duì)接了蛋白質(zhì)信息和核酸信息,是分子生物學(xué)研究中一個(gè)里程碑事件。部分氨基酸由多種不同類(lèi)型的同義密碼子所編碼,這使得編碼相同蛋白質(zhì)的基因可能具有完全不同的密碼子使用模式。而同義密碼子的偏好性使用在轉(zhuǎn)錄、翻譯水平上影響著基因的表達(dá)。在共翻譯蛋白質(zhì)折疊過(guò)程中,密碼子的偏好性使用改變了蛋白質(zhì)的構(gòu)象,從而導(dǎo)致其功能的分化。不僅如此,m RNA的穩(wěn)定性,癌癥和其他疾病的發(fā)生與密碼子的使用模式相關(guān)。隨著后基因組時(shí)代的到來(lái),從公共數(shù)據(jù)庫(kù)中可以獲取海量的基因組和轉(zhuǎn)錄組數(shù)據(jù)。如何分析利用已有的數(shù)據(jù),為實(shí)驗(yàn)研究提供參考,是目前生物信息學(xué)研究的重點(diǎn)內(nèi)容之一。薔薇目?浦参锎ㄉ(Morus notabilis)的基因組測(cè)序,為其他薔薇目植物的研究提供了豐富的基因數(shù)據(jù)。桑樹(shù)本身適應(yīng)性強(qiáng),在全球有廣泛的分布,并且具有很高的食用藥用價(jià)值。本研究對(duì)川桑密碼子進(jìn)行了較為全面的生物信息學(xué)分析。主要研究結(jié)果如下:1.川桑葉綠體基因組密碼子分析對(duì)川桑葉綠體基因組的研究發(fā)現(xiàn),選擇壓力作用于基因的密碼子使用。對(duì)十五個(gè)薔薇目物種的葉綠體的研究表明,薔薇目植物間的葉綠體基因核酸組成十分近似。物種間密碼子使用模式的相似性與物種的親緣關(guān)系不完全一致,表明選擇壓力作用于一些物種中的一些基因使得相近物種的密碼子使用模式呈現(xiàn)出較大的差異。薔薇目物種葉綠體基因密碼子使用普遍受到選擇作用,川桑相較而言受到了最弱的自然選擇。2.川桑核基因組密碼子分析對(duì)川桑核基因組密碼子使用模式的分析鑒定出了川桑中的高頻密碼子和最優(yōu)密碼子。結(jié)合轉(zhuǎn)錄組數(shù)據(jù)分析發(fā)現(xiàn),川桑的最優(yōu)密碼子的使用比例隨著基因的表達(dá)水平升高而升高,這種現(xiàn)象在持家基因中表現(xiàn)尤為明顯。對(duì)影響川桑密碼子使用的潛在因素分析后發(fā)現(xiàn),基因的堿基組成、長(zhǎng)度、表達(dá)量和編碼氨基酸的分子量均會(huì)影響同義密碼的偏好性使用。在進(jìn)行多重相關(guān)分析時(shí)發(fā)現(xiàn),川桑中高表達(dá)基因具有長(zhǎng)度短,強(qiáng)的密碼子偏好性,高的GC含量,偏好使用低分子量和合成成本更低的氨基酸的特點(diǎn)。對(duì)其密碼子偏好性觀測(cè)值與預(yù)測(cè)值差異較大的基因分析后發(fā)現(xiàn),涉及核苷酸代謝、能量代謝、轉(zhuǎn)錄、翻譯等過(guò)程的基因往往更容易受到選擇作用從而呈現(xiàn)出更強(qiáng)的密碼子偏好性,這意味著基因功能與密碼子使用模式似乎存在一定的聯(lián)系。進(jìn)行交互信息分析后發(fā)現(xiàn),僅在涉及嘧啶代謝、嘌呤代謝和RNA聚合酶等過(guò)程的基因中存在大量密碼子具有基因功能特異的密碼子使用模式,而其他功能的基因沒(méi)有十分獨(dú)特的密碼子使用模式。研究發(fā)現(xiàn)持家基因中密碼子偏好性與基因表達(dá)水平有一個(gè)較好的對(duì)應(yīng)關(guān)系,近年在人的基因中發(fā)現(xiàn)類(lèi)似的現(xiàn)象并提出了持家基因的密碼子可能受到更顯著的翻譯選擇。研究中發(fā)現(xiàn)基因的表達(dá)水平影響著基因的密碼子偏好性,川桑中持家基因的表達(dá)水平明顯高于組織表達(dá)特異基因和其他基因。比較了表達(dá)水平近似的持家基因和其他基因后仍然得到類(lèi)似的結(jié)果,表明在持家基因中密碼子受到明顯的選擇。密碼子上下文偏好同樣在川桑中被觀察到。有趣的是這種密碼子上下文偏好性受基因表達(dá)水平的影響,不僅相鄰密碼子之間存在偏好性,密碼子在基因中的位置同樣影響著同義密碼子的偏好性使用。基因起始區(qū)域偏好使用簡(jiǎn)并位點(diǎn)為C的密碼子,而回避使用簡(jiǎn)并位點(diǎn)為U的密碼子。簡(jiǎn)并位點(diǎn)為C的密碼子在不同基因中呈現(xiàn)出較為一致的使用趨勢(shì),而其他的密碼子基于位置的偏好性并不十分一致。盡管存在基于位置的密碼子偏好性,但是這種偏好性似乎沒(méi)有使得川;虻恼郫B能量與同義密碼子空模型之間存在顯著差異。3.帶有用戶(hù)界面的密碼子分析軟件Codons Box的開(kāi)發(fā)整理本研究中經(jīng)常使用的功能,使用Java開(kāi)發(fā)帶有友好用戶(hù)界面的密碼子分析工具Codons Box。這使后續(xù)密碼子分析可以回避部分重復(fù)性的工作,研究者可以專(zhuān)注于更為深入和個(gè)性化的密碼子研究。Codons Box的網(wǎng)絡(luò)地址為:https://github.com/cqwenyan/Codons Box,該軟件將為相關(guān)領(lǐng)域的研究提供幫助。川桑密碼子的研究為其他植物的相關(guān)分析提供了基礎(chǔ)資料,也為桑樹(shù)轉(zhuǎn)基因和育種研究提供了基礎(chǔ)數(shù)據(jù)。開(kāi)發(fā)得到的工具為密碼子分析提供了簡(jiǎn)單高效的方法,方便其他物種中密碼子的個(gè)性化研究。
[Abstract]:The codon is the three continuous nucleotides on M RNA, the law of nucleotide encoding amino acids at the time of synthesis of proteins. The deciphering of the genetic code is a milestone in molecular biology research. Some amino acids are encoded by a variety of synonymous codons, which makes the encoding of the same egg. The genes of white matter may have completely different codon usage patterns. The preference of synonymous codons is used in transcription and the level of translation affects the expression of genes. In the process of CO translational protein folding, the preference of codons changes the conformation of the protein, resulting in its functional differentiation. Not only that, the stability of M RNA is stable. Qualitative, cancer and other diseases are related to the usage patterns of codons. With the arrival of the post genome era, a large number of genome and transcriptome data can be obtained from the public database. How to analyze and utilize the existing data to provide reference for experimental research is one of the key contents of bioinformatics research. The genome sequencing of the mulberry plant, Kasan (Morus notabilis), provides rich genetic data for the study of other Rosa plants. The mulberry tree itself has a wide distribution in the world and has a high edible and medicinal value in the world. This study has carried out a more comprehensive bioinformatics analysis on the codons of the mulberry. The results are as follows: 1. the study of the chloroplast genome of the mulberry chloroplast genome has found that the selection pressure is used to use the codon in the gene. The study of chloroplasts of fifteen species of Rosa species shows that the nucleic acid composition of the chloroplast gene among the Rosa plants is very similar. The similarity of the codon usage pattern among species is similar. The genetic relationship with species is not exactly the same, indicating that the selection of some genes in some species makes the codon usage patterns of similar species quite different. The use of the chloroplast gene codons in the Rosa species is generally selected. With the analysis of codon analysis of group codon analysis, the high frequency codon and the best codon are identified in the codon of the nuclear genome of Morus. Combined with the analysis of transcriptional data, it is found that the ratio of the best codon is increased with the increase of gene expression level. This phenomenon is particularly evident in the housekeeping gene. The analysis of the potential factors affecting the use of codon found that the base composition, length, expression of the gene and the molecular weight of the encoded amino acids all affect the preference of the synonymous ciphers. In the multicorrelation analysis, the high expression genes in the mulberry were found to have short length, strong codon preference, high GC content, and preferred use. The characteristics of an amino acid with low molecular weight and lower cost of synthesis. Gene analysis, which differs from the predicted values of their codon preference, finds that genes involved in nucleotides metabolism, energy metabolism, transcription, translation and other processes tend to be more likely to be selected to present a stronger codon preference, which means genes. There seems to be a connection between the function and the codon usage pattern. After the analysis of interactive information, it is found that there are a large number of codon in the genes involving pyrimidine metabolism, purine metabolism and RNA polymerase, which have genetic function specific codon usage patterns, while other active genes do not have a very unique codon usage model. The study found that there is a good correspondence between the codon preference and the gene expression level in the housekeeping gene. In recent years, similar phenomena have been found in human genes and the codon of the family gene may be more significantly translated. The expression level of the housekeeping gene was significantly higher than that of the specific gene and other genes in the tissue. The similar results were still obtained after the homemaking and other genes of the approximate expression level, indicating that the codons in the housekeeping genes were obviously selected. The codon context preference was observed in the mulberry. Codon context preference is influenced by the level of gene expression, not only between adjacent codons, but the location of codon in the gene also affects the preference of synonymous codons. The gene initiating region favours the codon with the degenerate site as C and avoids the use of the degenerate U codon. The degeneracy site is C The codon presents a more consistent use trend in different genes, while other codons are not very consistent in position based preference. Although there is a position based codon preference, this preference does not seem to make significant differences between the folding energy of the mulberry gene and the synonymous codon empty model.3. Codons Box, a cipher analysis software with a user interface, has developed the functions often used in this study, using Java to develop a codon analysis tool with friendly user interface, Codons Box., which enables subsequent codon analysis to avoid partial duplication, and researchers can focus on more in-depth and personalized passwords. The network address of.Codons Box is: https://github.com/cqwenyan/Codons Box, which will help the research in the related fields. The research of the codon of the sonson provides basic data for the related analysis of other plants, and provides basic data for the study of mulberry transgenic and breeding. The developed tools are the codons. Analysis provides a simple and efficient method to facilitate the personalized research of codon in other species.
【學(xué)位授予單位】:西南大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類(lèi)號(hào)】:S888.2;Q943.2

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