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Bioinformatic Mining and Analysis of Genetic Elements in Genomes

Posted on:2014-08-28Degree:Ph.DType:Dissertation
University:The Chinese University of Hong Kong (Hong Kong)Candidate:Huang, QianliFull Text:PDF
GTID:1450390005990980Subject:Biology
Abstract/Summary:
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.
Keywords/Search Tags:Genomes, Elements, GIST, PTM, Mushroom-forming, Genomic
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