在海量的生物數據中發掘重要的功能元件、揭示其功能特徵及相應的潛在生物機制是後基因組時代的一個巨大的挑戰。這裡，以特定的基因組為對象，運用生物信息學的理論與方法，對基因組島及後翻譯修飾系統進行了系統的挖掘、分析。 / 首先，收集源於7個真核生物的超過70,000個試驗驗證的翻譯後修飾事件。對照不帶有任何後翻譯修飾靶點的蛋白, 對受多種翻譯後修飾調控的蛋白 (MTP-蛋白) 的特性和功能進行了分析比較。(1) MTP-蛋白顯著傾向於形成蛋白質複合物，並能與更多的蛋白質相互作用，同時偏好於在蛋白質-蛋白質相互作用網絡中擔當樞紐。(2) MTP-蛋白還具有獨特的功能偏好以及特定的亞細胞定位。(3) 約80的後翻譯修飾位點位於蛋白的無序區域。同時MTP-蛋白比不受後翻譯修飾調控的蛋白擁有更多的無序區域。(4) 擁有較少無序區域的MTP-蛋白主要和蛋白質-DNA複合物的形成相關。(5) 只有一小部分單個後翻譯修飾事件對結合能的影響大於2kcal/mol，但組合的多種後翻譯修飾，如磷酸化加上乙酰化, 對結合能的影響大 幅提升。 / 隨後，對74真菌基因組中泛素化系統的不同組件(分別為泛素，E1，E2，E3和E3的底物) 進行註釋並比較分析。 (1) 與擔子菌的其他基因組相比, 菇類基因組中具有顯著多的泛素。 (2) 儘管E1的數目在目標基因組之間波動極小, 菇類基因組中E2的數目仍顯著高於其他擔子菌。 (3) 對於候選的E3，菇類基因組中Paracaspase和F-box的數目也顯著高於其他擔子菌。這些結果表明，泛素化系統很可能在真菌形態分化、尤其是菇的形成中扮演著重要角色。 / 然後，與全基因組相比，發現基因組島具有顯著高的轉錄起始信號富集. 基於這種特異的轉錄調控信號，設計了一個新的基因組島預測程序(命名GIST)。通過分析顯示GIST具有較高的靈敏度和準確性. 最後，運用GIST，對最近在德國暴發的菌株TY-2482中的基因組島進行了首次的檢測和分析。 / 總之，這些工作不僅大大拓展了我們關於特定功能元素的理解，如MTP-蛋白和基因組島，同時也為進一步的相關研究提供了重要的工具和線索，如GIST以及菇類基因組中的泛素化系統。 / In the post-genomic era, it is a huge challenge to detect the functional elements in the "ocean" of data and provide meaningful biological inferences. Here, many interesting functional elements have been characterized and analyzed among targeted genomes. / First, through compiling more than 70,000 experimentally determined posttranslational modification (PTM) events from 7 eukaryotic organisms, the features and functions of proteins regulated by multiple types of PTMs (Mtp-Proteins) are detected and analyzed by compared with proteins harboring no known target site of PTMs. (1) The Mtp-Proteins are found significantly enriched in protein complexes, having more protein partners and preferred to act as hubs in protein-protein interaction network. (2) Mtp-Proteins also possess distinct function focus and biased subcellular locations. (3) Overall, about 80% analyzed PTM events are embedded in intrinsic disordered regions (IDRs). And most Mtp-Proteins have more IDRs than proteins without PTM sites. It suggests IDR may account most for why some proteins can harbor so many extraordinary functions. (4) Interestingly, some particular Mtp-Proteins biased carrying PTMs located in ordered regions are observed mainly related to "protein-DNA complex assembly". (5) We further evaluated the energetic effects of PTMs on stability of PPI and found that only a small fraction of single PTM event influence the binding energy more than 2kcal/mol; but combinational use of PTM types i.e. combinational phosphorylation and acetylation can change the binding energy dramatically. / On the second part, the different components in ubiquitination system, respectively ubiquitin, E1, E2, E3 and the substrates of E3, are identified and analyzed comparatively across 74 fungi genomes. The results mainly include: (1) the ubiquitin number is significantly higher within the mushroom-forming genomes compared to other basidiomycota genomes. (2) The number of E1, with the average of 2.92, is consistent among most genomes. However, the number of E2 is different between mushroom-forming genomes and other basidiomycota genomes. (3) For the E3 candidates, it is found that the number of domain Paracaspase and F-box in the mushroom-forming genomes is significantly higher than the other basidiomycota genomes. These results suggest that the ubiquitination system may play vital role in divergence of fungi morphogenesis, especially, such as the formation of mushroom. / Then, the focus shift to genomic islands (GIs). Compared to the whole genome, highly enriched transcription initiation positions are firstly found to be precipitated in GI regions. Based on this heterogeneous transcriptional regulatory signal, a novel procedure GIST (Genome-island Identification by Signals of Transcription) for genomic island detection is designed. Interestingly, our method demonstrates higher sensitivity in detecting genomic islands harboring genes with biased GI-like function, preferenced subcellular localization, skewed GC property and shorter gene length. Finally, using the GIST, many interesting GIs are detected and analyzed in the German outbreak strain TY-2482 for the first time. / In summary, these work not only considerably expand our understanding of several functional genetic elements, such as genomic island and proteins regulated by combinational multiple PTMs, but also provide important tool and clues, such as GIST and potential E3 expansion in mushroom-forming fungi, for further related studies. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Huang, Qianli. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 161-186). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese. / Abstract --- p.i / 論文摘要 --- p.iii / Abbreviations --- p.v / Acknowledgements --- p.vi / Declaration --- p.viii / Table of Contents --- p.ix / List of Figures --- p.xi / List of Tables --- p.xiv / Chapter Chapter 1 --- Literature Review --- p.1 / Chapter 1.1 --- General introduction --- p.1 / Chapter 1.2 --- Post-translational modification --- p.2 / Chapter 1.2.1 --- Combinational multiple types of post-translational modification --- p.2 / Chapter 1.3 --- Genomic islands --- p.7 / Chapter 1.3.1 --- Brief introduction --- p.7 / Chapter 1.3.2 --- Bioinformatic tools and database for identification of Genomic islands --- p.9 / Chapter 1.4 --- Objectives and significance --- p.13 / Chapter Chapter 2 --- Systematic analysis on features and functions of proteins regulated by combinational multiple types of post-translational modifications --- p.15 / Chapter 2.1 --- Introduction --- p.15 / Chapter 2.2 --- Materials and Methods --- p.18 / Chapter 2.2.1 --- Annotation of PTM pattern and analyses on target residues --- p.18 / Chapter 2.2.2 --- Classification of Human Proteins --- p.19 / Chapter 2.2.3 --- Dataset of human protein-protein interactions (PPIs) and Construction of PPI network --- p.19 / Chapter 2.2.4 --- Calculation of Binding Energy --- p.20 / Chapter 2.2.5 --- Functional characterization and subcellular localization analysis --- p.21 / Chapter 2.2.5 --- Annotating IDR regions --- p.22 / Chapter 2.2.7 --- Statistical analyses --- p.23 / Chapter 2.3 --- Results --- p.23 / Chapter 2.3.1 --- Combinational interactions of multiple PTM types are undergoing evolutionary selection --- p.23 / Chapter 2.3.2 --- Evolutionary profile of modified amino acid residues --- p.33 / Chapter 2.3.3 --- Mtp-Proteins are enriched in the protein complex --- p.43 / Chapter 2.3.4 --- Multiple PTMs enable target protein function as hub or super-hub in PPI network --- p.46 / Chapter 2.3.5 --- Energetic effect of PTMs on the Stability of protein-protein binding --- p.60 / Chapter 2.3.6 --- Mtp-Proteins demonstrate distinct function focus --- p.65 / Chapter 2.3.7 --- Mtp-Proteins: located preferedly in Cytoplasm and Nucleus --- p.69 / Chapter 2.3.8 --- Why Mtp-Proteins possess so many special features : importance of IDR --- p.75 / Chapter 2.4 --- Discussion --- p.82 / Chapter 2.4.1 --- The hints from the features of Mtp-Proteins --- p.82 / Chapter 2.4.2 --- The implication of combinational interaction between two different functional PTM categories: biased locating in IDRs and ordered regions respectively --- p.84 / Chapter Chapter 3 --- Genome-wide comparative analyses of ubiquitome among basidiomycota and other typical fungi genomes --- p.87 / Chapter 3.1 --- Introduction --- p.87 / Chapter 3.2 --- Materials and Methods --- p.89 / Chapter 3.2.1 --- Genome sequences and annotation acquirement. --- p.89 / Chapter 3.2.2 --- Bioinformatic prediction of components in ubiquitome --- p.89 / Chapter 3.3 --- Results --- p.90 / Chapter 3.3.1 --- Identification of ubiquitin candidates among 74 fungi genomes --- p.90 / Chapter 3.3.2 --- Detection of potential E1 and E2 among all considered genomes --- p.94 / Chapter 3.3.3 --- Prediction and comparative analysis of different types of E3 --- p.98 / Chapter 3.3.4 --- The possible substrates of E3 --- p.104 / Chapter 3.4 --- Discussion --- p.107 / Chapter Chapter 4 --- Genomic islands Identification by Signals of Transcription --- p.109 / Chapter 4.1 --- Introduction --- p.109 / Chapter 4.2 --- Materials and Methods --- p.112 / Chapter 4.2.1 --- Genome sequence and annotation data --- p.112 / Chapter 4.2.2 --- Transcription start points (TSPs) scanning --- p.113 / Chapter 4.2.3 --- Genomic island dataset construction --- p.114 / Chapter 4.2.4 --- GIST: Genomic-island Identification by Signal of Transcription --- p.115 / Chapter 4.2.5 --- Functional characterization and subcellular localization analysis --- p.116 / Chapter 4.2.6 --- Codon usage, GC content and gene length --- p.117 / Chapter 4.2.7 --- Statistical analyses --- p.118 / Chapter 4.3 --- Results --- p.132 / Chapter 4.3.1 --- High-density transcriptional initiation signals associated with GIs --- p.132 / Chapter 4.3.2 --- Predict the potential novel GIs through GIST: Genomic-island Identification by Signal of Transcription --- p.134 / Chapter 4.3.3 --- Comparative Analysis: Distribution of gene function categories --- p.138 / Chapter 4.3.4 --- Comparative Analysis: Divergence of subcellular locations --- p.140 / Chapter 4.3.5 --- Comparative Analysis: GC property and gene length --- p.144 / Chapter 4.3.6 --- Hints of "non-optimal" codon usage bias --- p.145 / Chapter 4.3.7 --- Application of GIST to analyze GIs in the German E. coli O104:H4 outbreak strain --- p.147 / Chapter 4.4 --- Discussion --- p.152 / Chapter Chapter 5 --- Concluding remarks --- p.158 / References --- p.161
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_328273 |
| Date | January 2013 |
| Contributors | Huang, Qianli., Chinese University of Hong Kong Graduate School. Division of Life Sciences. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography |
| Format | electronic resource, electronic resource, remote, 1 online resource (xiv, 186 leaves) : ill. (chiefly col.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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