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Thesis (PhD)--Stellenbosch University, 2025.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : Stellenbosch University
2025
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| _version_ | 1867613941855682560 |
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| access_status_str | Open Access |
| author | Dakurah, Ottovon Bismark |
| author2 | Patterton, Hugh-George |
| author_browse | Dakurah, Ottovon Bismark Patterton, Hugh-George |
| author_facet | Patterton, Hugh-George Dakurah, Ottovon Bismark |
| author_sort | Dakurah, Ottovon Bismark |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2025. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/134581 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:44:08.546Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/134581 Identification of a possible sequence of structural events associated with genome evolution Dakurah, Ottovon Bismark Patterton, Hugh-George Stellenbosch University. Faculty of Science. Centre for Bioinformatics and Computational Biology. Genomics Comparative genomics Saccharomyces cerevisiae -- Genetics -- Computer simulation Genomes -- Evolution -- Mathematical models Bioinformatics -- Computer simulation Computational biology -- Mathematical models UCTD Thesis (PhD)--Stellenbosch University, 2025. Dakurah, O. 2025.Identification of a possible sequence of structural events associated with genome evolution. Unpublished doctoral dissertation. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/847245e1-4946-4f38-8c28-cd4903023a02 ENGLISH ABSTRACT: The precise order, quantity, and nature of genomic rearrangements required to convert one genome into another serve as fundamental parameters in comparative evolutionary genomics. Current computational models for studying these transformations frequently omit biological constraints, resulting in systematic errors such as miscalculations of rearrangement frequencies. To address this gap, we present Genolve+, an open-source command-line tool that incorporates two critical biological parameters: intergenic region length conservation and three-dimensional chromatin spatial proximity. This framework enables more precise reconstruction of evolutionary trajectories between closely related genomes. Application of Genolve+ to Saccharomyces cerevisiae lineages (a forest strain and its domesticated counterpart) revealed 13 evolutionary events required for genomic transformation: 9 conservative (7 translocations, 1 fission, 1 fusion) and 4 non-conservative (2 insertions, 2 deletions), yielding a minimal edit distance of 13. Conservative events dominated evolutionary dynamics, contributing disproportionately to reduced genomic divergence, while non-conservative events incurred greater evolutionary "cost." Notably, these rearrangements localized to distinct genomic loci: recombination hotspots (associated with sequence-driven instability) and three-dimensional chromatin contact regions (linked to spatial genome organization). This spatial specificity underscores the dual influence of sequence context and higher-order nuclear architecture in shaping evolutionary pathways. The analysis revealed a strong correlation between recombination hotspots, regions of three-dimensional chromatin contact, and histone modification patterns in the S. cerevisiae genome. Notably, 25% to 100% of all identified recombination hotspots coincided with H3K9-enriched regions, demonstrating significant enrichment (p < 0.001). The analysis further demonstrated that the number of recombination hotspots per chromosome scaled proportionally with chromosome length, while three-dimensional chromatin contact regions showed no dependence on chromosome size. Additionally, recombination hotspots were preferentially localized near genomic loci marked by increased chromatin accessibility. Together, these findings highlight the integral relationship between 3D genome organization, chromatin state, and mechanisms driving chromosomal recombination and evolutionary adaptation. In summary, integrating biological constraints into computational evolutionary models significantly enhances their predictive power and biological relevance. Our findings indicate that conservative genomic events exert a greater influence on genome evolution compared to non-conservative processes. Notably, recombination hotspots and three-dimensional chromatin architecture—features conserved across large genomic scales—are tightly linked to evolutionary dynamics, with H3K9ac modification emerging as a pivotal regulator of genomic evolution. These insights collectively underscore the interplay between spatial genome organization, epigenetic marks, and evolutionary adaptation. AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar. Doctoral 2025-12-15T08:39:31Z 2025-12-15T08:39:31Z 2025-12 Thesis https://scholar.sun.ac.za/handle/10019.1/134581 en Stellenbosch University xv, 181 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Genomics Comparative genomics Saccharomyces cerevisiae -- Genetics -- Computer simulation Genomes -- Evolution -- Mathematical models Bioinformatics -- Computer simulation Computational biology -- Mathematical models UCTD Dakurah, Ottovon Bismark Identification of a possible sequence of structural events associated with genome evolution |
| title | Identification of a possible sequence of structural events associated with genome evolution |
| title_full | Identification of a possible sequence of structural events associated with genome evolution |
| title_fullStr | Identification of a possible sequence of structural events associated with genome evolution |
| title_full_unstemmed | Identification of a possible sequence of structural events associated with genome evolution |
| title_short | Identification of a possible sequence of structural events associated with genome evolution |
| title_sort | identification of a possible sequence of structural events associated with genome evolution |
| topic | Genomics Comparative genomics Saccharomyces cerevisiae -- Genetics -- Computer simulation Genomes -- Evolution -- Mathematical models Bioinformatics -- Computer simulation Computational biology -- Mathematical models UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/134581 |
| work_keys_str_mv | AT dakurahottovonbismark identificationofapossiblesequenceofstructuraleventsassociatedwithgenomeevolution |