原核生物基因组寡核苷酸转移概率偏倚的物种特异性及致病关联性

发布时间：2018-01-09 05:05

本文关键词：原核生物基因组寡核苷酸转移概率偏倚的物种特异性及致病关联性　出处：《华南理工大学》2012年硕士论文　论文类型：学位论文

【摘要】：寡核苷酸使用模式及偏倚是基因组组成的一个重要特征，体现了个体的全部遗传信息在碱基水平上的分布，部分寡核苷酸的过量出现可能会导致一些遗传性疾病的发生。然而，关于寡核苷酸使用模式的偏倚是否具有种群特异性并反映种群的生物学特征这一问题，尚未阐明。鉴于此，本文基于一阶马尔可夫链模型，提出了一个度量寡核苷酸使用模式偏倚的新指标—－基因组三核苷酸（trinucleotide, tri-）转移概率偏倚（transitionprobability bias, TPB）特征向量，或称之为三核苷酸转移概率最大偏倚分布，并利用该指标研究了原核生物基因组组成和分布的偏倚特征，及其与菌株的生物学特征的关联性。主要研究内容包括以下四个方面：一、通过分析727条有代表性的原核生物基因组序列间tri-TPB特征向量的相关性，研究了不同的原核生物基因组间三核苷酸转移概率最大偏倚分布的相似性，以及这种相似性与序列的G+C含量之间的关系。首次发现：基因组tri-TPB特征向量具有物种特异，亲缘关系越近的物种，它们的tri-TPB特征向量越相似；同种内的不同菌株具有几乎完全相同的tri-TPB特征向量，并且不依赖于基因组的G+C含量。二、通过分析原核生物基因组与其质粒序列、噬菌体序列以及水平转移基因之间tri-TPB特征向量的相关性，发现与原核生物基因组进化密切相关的外源性基因元素，它们与宿主基因组之间tri-TPB特征向量的相关性高于与其他非宿主基因组的相关性，，且这种相关性随着亲缘关系的逐渐疏远而逐渐减小。三、通过对具有不同宿主的33个dsDNA和dsRNA病毒的基因组tri-TPB特征向量进行相关性分析，发现病毒基因组与原核生物基因组的三核苷酸转移概率偏倚的分布特征不同，即病毒基因组tri-TPB特征向量不具有种内特异性，且它们的三核苷酸转移概率最大偏倚的差异与宿主的特异性无关。四、分析了具有不同的致病性特征以及具有不同宿主的近缘细菌基因组间tri-TPB特征向量的相关性，并将其与基于SSU rRNA基因序列的传统系统发育分析结果进行比较。我们发现，基因组tri-TPB特征向量的相似性与菌株的致病性或宿主的特异性等生物学特征相关联，而这种关联性通常不能从传统的系统发育分析中获得，并可能被传统分析方法所曲解。本研究建立了一套基于三核苷酸转移概率最大偏倚的基因组组成和分布的分析方法，确立了原核生物基因组tri-TPB向量的物种特异性和致病特征的关联性，为基于全基因组寡核苷酸组成和分布信息的物种及其致病性的进化分析提供了新的思路。
[Abstract]:The usage pattern and bias of oligonucleotides is an important feature of genome composition, which reflects the distribution of all genetic information of individuals at base level. The excessive occurrence of partial oligonucleotides may lead to the occurrence of some hereditary diseases. However, the question of whether the bias of the use pattern of oligonucleotides is population specific and reflects the biological characteristics of the population. In view of this, based on the first-order Markov chain model, a new index to measure the bias of oligonucleotide usage pattern, genomic trinucleotide, is proposed. The transition probability bias (TPB) eigenvector is known as the maximum bias distribution of trinucleotide transfer probability. The bias characteristics of the genomes composition and distribution of prokaryotes and their relationship with the biological characteristics of the strain were studied by using this index. The main contents of the study included the following four aspects: One is to analyze the correlation between tri-TPB eigenvector of 727 representative prokaryotes. The similarity of maximum bias distribution of trinucleotide transfer probability among different prokaryotes was studied. And the relationship between the similarity and the G C content of the sequence. For the first time, it was found that the genome tri-TPB characteristic vector had species-specific, and the closer the genetic relationship was, the more close the species was. The more similar their tri-TPB Eigenvectors are; Different strains of the same species have almost identical tri-TPB Eigenvectors and do not depend on the G C content of the genome. Secondly, the correlation of tri-TPB characteristic vectors between the prokaryote genome and its plasmid sequence, phage sequence and horizontal transfer gene was analyzed. The exogenous gene elements closely related to the evolution of prokaryote genomes were found to have a higher correlation with the tri-TPB characteristic vectors between the host genomes than with other non-host genomes. And this correlation gradually decreased with the gradual alienation of the kinship. Thirdly, the genomic tri-TPB characteristic vectors of 33 dsDNA and dsRNA viruses with different hosts were analyzed. It was found that the distribution characteristics of trinucleotide transfer probability bias of virus genome and prokaryote genome were different, that is, the tri-TPB characteristic vector of virus genome had no intraspecific characteristics. The difference in the maximum bias of the trinucleotide transfer probability was independent of the host specificity. Fourthly, the correlation of tri-TPB characteristic vectors among the genomes of relative bacteria with different hosts and different pathogenicity was analyzed. The results of phylogenetic analysis based on SSU rRNA gene sequence were compared. The similarity of genomic tri-TPB feature vectors is associated with biological characteristics such as pathogenicity or host specificity, which is not usually derived from traditional phylogenetic analysis. And may be misinterpreted by traditional analytical methods. In this study, a set of methods for the analysis of genome composition and distribution based on the maximum bias of trinucleotide transfer probability were established. The relationship between species-specificity and pathogenicity of tri-TPB vector of prokaryote genome was established. It provides a new idea for the evolutionary analysis of species and their pathogenicity based on the information of oligonucleotide composition and distribution.
【学位授予单位】：华南理工大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R346

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