基于转录组学探究猪基因表达特征及其调控网络

发布时间：2018-05-13 01:08

本文选题：猪 + 共调控　；参考：《石河子大学》2017年硕士论文

【摘要】：生物机体是一个精美的体系,参与生命活动的物质环环相扣,形成一个复杂的网络系统。利用网络生物学的技术,提炼高通量基因表达数据,已经成为研究基因互作及功能机制的重要方向。本研究旨在利用猪的基因组和转录组数据,分析猪的基因表达特征,解析基因的网络调控模式,为探究猪特有的基因资源信息,提供新思路和新途径。获得以下主要结果:(1)利用猪的RNA-seq数据集,鉴定了3,136个持家基因和1,316个组织特异性基因;对比显示,持家基因结构比组织特异性基因紧凑,受到较强净化选择压力;持家基因启动子区域比组织特异性基因保守,其表达调控的复杂性低于组织特异性基因,表明持家基因的进化缓慢稳定,持家基因主要与细胞的基础代谢功能相关,组织特异性基因主要与组织分化、发育、环境适应相关的特性一致。(2)对比猪与人的持家基因,发现二者交集较低,猪持家基因结构显著长于人持家基因;然而,功能富集和蛋白活性位点分析,显示尽管二者持家蛋白之间的同源性低且空间结构有异,但却具有相似的蛋白质活性位点、侧链、催化中心或DNA结合域,表现趋同进化。(3)基于权重基因共表达网络分析技术,利用猪多个组织的RNA-seq数据集,构建了24个基因共表达模块;对模块进行富集分析,发现模块具有功能特异性,并且模块内许多基因的启动子含有相似的顺式作用元件,显示模块内的基因呈显著协同关系;此外,模块具有组织特异性,如与SIX1、PRKAG3等基因相关的局部网络涉及肌肉发育。(4)利用猪肌肉组织的RNA-seq数据集,构建了13个网络模块;功能富集和组织定位分析,显示大部分模块都与肌肉组织的分化、发育和代谢功能相关;调控模体富集分析,显示模块内基因的启动子,显著富集一个或几个的顺式作用元件,对应于POU3F3、FOXC2、Sox18等17个转录因子结合位点,揭示了转录因子与其靶基因集的调控关系。优异基因资源的挖掘是提高猪生产力的有效途径之一。在转录组水平上,本研究探索了猪的基因表达特征,鉴定了持家基因与组织特异基因集,并揭示了持家基因的趋同进化模式;所建立的基因共表达网络,揭示了许多与功能相关的候选基因,可为探究中国地方猪品种特有的基因资源信息、丰富分子育种理论奠定基础。
[Abstract]:Biological organism is a delicate system. The matter involved in life activities is linked to each other, forming a complex network system. Using network biology technology to extract high throughput gene expression data has become an important research direction in gene interaction and functional mechanism. The purpose of this study was to analyze the gene expression characteristics of pigs by using the genomic and transcriptional data of pigs, and to analyze the network regulation model of genes, so as to provide new ideas and approaches for exploring the information of porcine specific gene resources. The main results were as follows: 1) 3136 housekeeping genes and 136 tissue-specific genes were identified by using RNA-seq data sets of pigs, and the results showed that the housekeeping genes were more compact than tissue specific genes and were under strong pressure of purification and selection. The promoter region of housekeeping gene is more conserved than that of tissue specific gene, and the complexity of its expression regulation is lower than that of tissue specific gene, which indicates that the evolution of housekeeping gene is slow and stable, and the housekeeping gene is mainly related to the basic metabolic function of cell. Tissue specific genes are mainly related to tissue differentiation, development and environmental adaptation. (2) comparing pig and human housekeeping genes, we found that the structure of pig housekeeping genes is significantly longer than that of human housekeeping genes. Functional enrichment and protein activity site analysis showed that although the homology and spatial structure of the two homekeeping proteins were low, they had similar protein active sites, side chains, catalytic centers or DNA binding domains. Based on the technique of weight gene coexpression network analysis, 24 gene coexpression modules were constructed by using RNA-seq data sets of multiple tissues of pigs, and the functional specificity of the modules was found by enrichment analysis. And the promoter of many genes in the module contains similar cis-acting elements, which shows that the genes in the module are significantly synergistic; in addition, the module is tissue specific. For example, the local network related to SIX 1, PRKAG3 and other genes involved in muscle development. (4) using the RNA-seq data set of pig muscle tissue, 13 network modules were constructed, and the function enrichment and tissue localization analysis showed that most of the modules were differentiated with muscle tissue. Regulation motif enrichment analysis showed that the promoter of the gene in the module significantly enriched one or more cis-acting elements corresponding to 17 transcription factor binding sites, such as POU3F3F3FOXC2OX18, etc. The regulatory relationship between transcription factors and their target gene sets was revealed. The mining of excellent genetic resources is one of the effective ways to improve pig productivity. At the transcriptional level, this study explored the gene expression characteristics of pigs, identified housekeeping genes and tissue-specific gene sets, and revealed the convergent evolutionary patterns of housekeeping genes. Many candidate genes related to function are revealed, which can be used to explore the specific genetic resources of Chinese local pig breeds and enrich molecular breeding theory.
【学位授予单位】：石河子大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：S828;Q78

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