The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses

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dc.contributor.advisorMartin, Darren Pen_ZA
dc.contributor.authorMuhire, Brejnev Muhizien_ZA
dc.date.accessioned2016-02-09T12:16:37Z
dc.date.available2016-02-09T12:16:37Z
dc.date.issued2015en_ZA
dc.descriptionIncludes bibliographical referencesen_ZA
dc.description.abstractSecondary 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.en_ZA
dc.identifier.apacitationMuhire, B. M. (2015). <i>The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Institute of Infectious Disease and Molecular Medicine. Retrieved from http://hdl.handle.net/11427/16933en_ZA
dc.identifier.chicagocitationMuhire, Brejnev Muhizi. <i>"The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Institute of Infectious Disease and Molecular Medicine, 2015. http://hdl.handle.net/11427/16933en_ZA
dc.identifier.citationMuhire, B. 2015. The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Muhire, Brejnev Muhizi AB - 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. DA - 2015 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses TI - The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses UR - http://hdl.handle.net/11427/16933 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16933
dc.identifier.vancouvercitationMuhire BM. The evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA viruses. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Institute of Infectious Disease and Molecular Medicine, 2015 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/16933en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherBioinformaticsen_ZA
dc.titleThe evolutionary impacts of secondary structures within genomes of eukaryote-infecting single-stranded DNA virusesen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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