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Identification of a possible sequence of structural events associated with genome evolution

Thesis (PhD)--Stellenbosch University, 2025.

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Main Author: Dakurah, Ottovon Bismark
Other Authors: Patterton, Hugh-George
Format: Thesis
Language:English
Published: Stellenbosch : Stellenbosch University 2025
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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
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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 Unpublished doctoral dissertation.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