【作者】 林丹；

【导师】 郭锋彪；

【作者基本信息】 电子科技大学 ， 生物物理学， 2014， 硕士

【摘要】 微生物功能基因组学的功能分析无论对于微生物自身还是对于阐明高等生物的基因功能和进化特征都很重要。本课题通过对多种微生物的功能基因进行预测和分析,为微生物功能基因的预测和分析工作提供了新的思路和参考。本研究包括以下四个工作:(1)酵母基因组具有生物学意义的开放阅读框(ORFs)的数目一直悬而未决。运用支持向量机LibSVM结合六个生物特征量建立黄金模型对酿酒酵母基因组蛋白质编码基因进行预测。该法的准确性通过十重交叉验证(>99.5%)以及历史回顾对照得到了检验。该工作提供了相应的网络服务并为其它物种功能基因的预测提供了可靠的方法。(2)有研究发现基因的保守性与基因的功能性密不可分。本工作通过运用COG功能分类对DEG数据库中二十种原核生物的必需基因和高表达基因的功能分布进行分析,揭示了基因的功能性与其进化保守性之间的关联。(3)基因的水平转移是促进物种多样性的重要进化因素。本工作通过对DEG数据库中二十种有水平转移基因数据的原核物种的必需性、表达水平与水平转移的重叠度和相关性进行分析,从基因水平转移(HGT)的角度揭示了必需基因和高表达基因的进化特异性。(4)具有重要COG功能的保守基因和水平转移基因都具有复制链定位偏性,我们从该角度对微生物必需基因和高表达基因的进化保守性比较作了补充研究,发现从不同角度进行研究得出的结论也不同。另外对CAI使用局限性的讨论显示单纯用CAI来表示表达水平并不可靠。通过对酿酒酵母基因组的重注释工作,我们提供了一种成功运用支持向量机预测蛋白质编码基因的新方法;从COG功能分类和基因水平转移角度对必需基因和高表达基因的进化研究也为功能基因进化学贡献了新的思路。鉴于在第一个工作中对酿酒酵母基因组重注释取得的良好效果,我们可以试图将这种方法扩展到其他基因的预测当中,如高表达基因、必需基因等,从而为这些基因的相关功能研究提供可靠保障。更多还原

【Abstract】 The function analysis of the microbial functional genomics is of great importance to the clarification of the gene functions and evolutionary characters for microbes as well as higher organisms. By taking into the prediction and analysis of the fucntional genes of multiple microbes, we offer new thoughts to the accurate gene prediction and evolutionary studies to the microbial functional genes. This research mainly contains the following four parts:1. The annotation of the well-studied organism, Saccharomyces cerevisiae, keeps improving in the past decade while there are unresolved debates over the amount of biologically significant open reading frames(ORFs) in yeast genome. By combining the Support Vector Machine(SVM) method with six widely used measurements of sequence statistical features, we revisited the total count of protein-coding genes in S. cerevisiae S288 c genome. The accuracy of our method is over 99.5% in 10-fold cross-validation, and a retrospective examination showed the fidelity of our method in recognizing ORFs that likely encode proteins. In addition, we have provided a web service that can be accessed at http://cobi.uestc.edu.cn/services/yeast/. The method can be appied to the prediction of other kinds of functional genes.2. The essential genes and high expression of gene are two important evolutionary conservative genes. Studies have found that the conservation of the genes is inseparable with their functions. We got 20 prokaryotes from the DEG Database with essential genes available and analysis the functional distribution of both the essential genes and the high expression genes in these species. The study reveals the relationships between gene function and conservation.3. The horizontal gene transfer drives the diversity evolution of species. We analysis the overlaps and correlative coefficient between the essentiality genes, the high expression genes and the HGTs of the 20 prokaryotic species with DEG data. This work reveals the comparison of evolutionary strength between the essentiality and expression level of genes from the aspect of HGT.4. Considering both the COGs and the HGTs reflect replication strand bias, we make an additional study about the evolutionary comparison between the high expression genes and the essential genes from this aspect. In addition, we discussed the limitation of simply using CAI as a substitute of gene expression and found different results drawing from different angles. Both the essential genes and the high expression genes show codon usage optimization, revealing the two have gone through a strong evolutionary translation selection and it’s unreliable to simply use CAI to represent the expression level.By using the SVM to predict the coding genes of the S. cerevisiae S288 c, we provide a reliable method to predict the protein-coding genes in Saccharomyces genomes, and by using the COG functional classification and the horizontal gene transfer data, we offer new evidences to the evolutionary study of the essential genes and the high expression genes. Furthermore, given the high accuracy and reliability of the first re-annotation work, we may consider using support vector machine(SVM) with appropriate biological features to predict other functional genes, such as high expression genes, essential genes, etc, which will guarantee the further functional analysis of these genes.更多还原