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The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses
Includes bibliographical references
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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Institute of Infectious Disease and Molecular Medicine
2016
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| _version_ | 1867613255318372352 |
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| access_status_str | Open Access |
| author | Muhire, Brejnev Muhizi |
| author2 | Martin, Darren P |
| author_browse | Martin, Darren P Muhire, Brejnev Muhizi |
| author_facet | Martin, Darren P Muhire, Brejnev Muhizi |
| author_sort | Muhire, Brejnev Muhizi |
| collection | Thesis |
| description | Includes bibliographical references |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/16933 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:33:13.838Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2016 |
| publishDateRange | 2016 |
| publishDateSort | 2016 |
| publisher | Institute of Infectious Disease and Molecular Medicine |
| publisherStr | Institute of Infectious Disease and Molecular Medicine |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/16933 The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses Muhire, Brejnev Muhizi Martin, Darren P Bioinformatics Includes bibliographical references Secondary structures forming through base-pairing in virus genomes have been proven to regulate several processes during viral replication cycles, including genome replication, transcription, post-transcriptional activities, protein synthesis, genome packaging, generation of viral sub-genomes and evasion of host-cell immune responses. Although computational DNA/RNA folding methods based-on free energy minimisation approaches are capable of predicting structures that form within virus genomes, these methods are not entirely accurate. Notably, many of structures that are accurately predicted will likely have no biological importance within the genomes in which they reside because even randomly generated single-stranded RNA/DNA sequences will form stable secondary structures. Nevertheless, with additional genome evolution analyses involving the detection of natural selection, sequence co-evolution, and genetic recombination, it is possible to both validate the existence of, and infer the biological importance of, computationally predicted structures. Here I implement and deploy free bioinformatics tools to (1) automate nucleotide and protein sequences classification into datasets useful for downstream molecular evolution analyses; (2) improve the accuracy of computational virus-genome-scale secondary structure prediction; (3) enable the identification of biologically relevant secondary structures using signals of purifying selection, coevolution and recombination within aligned sequence datasets; and (4) enable efficient visualisation of structural and selection data for better characterisation of individual secondary structural elements. Using these tools I carried-out large scale studies that predicted and characterised novel functional secondary structures, that potentially regulate transcription, translation, gene splicing, and replication, within the genomes of eukaryote-infecting ssDNA viruses (Circoviridae, Anelloviridae, Parvoviridae, Nanoviridae, and Geminiviridae). I show that purifying selection tends to be stronger at base-paired sites than it is at unpaired sites and, wherever mutations are tolerable within paired regions, I demonstrate that there exist strong associations between base-pairing and complementary coevolution. Finally, I show that the recombinant genomes of some, but not all, eukaryote-infecting ssDNA virus groups display weak evidence of both homologous and non-homologous recombination break-points preferentially occurring at genome sites that minimally disrupt secondary structures. Altogether, these results suggest that natural selection acting to maintain important biologically functional secondary structural elements has been a major process during the evolution of eukaryote-infecting ssDNA viruses. 2016-02-09T12:16:37Z 2016-02-09T12:16:37Z 2015 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/16933 eng application/pdf Institute of Infectious Disease and Molecular Medicine Faculty of Health Sciences University of Cape Town |
| spellingShingle | Bioinformatics Muhire, Brejnev Muhizi The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses |
| thesis_degree_str | Doctoral |
| title | The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses |
| title_full | The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses |
| title_fullStr | The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses |
| title_full_unstemmed | The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses |
| title_short | The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses |
| title_sort | evolutionary impacts of secondary structures within genomes of eukaryote infecting single stranded dna viruses |
| topic | Bioinformatics |
| url | http://hdl.handle.net/11427/16933 |
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