Abstract
Subtelomeres are unique genomic regions with a highly variable molecular structure,characterised by abundant repetitive DNA sequences interspersed with functional genes. It is a transitional region between the telomere and the rest of the chromosome. The dynamic nature of the subtelomere sequences and constant shuffling contribute to genetic diversity and environmental adaptation among individuals. On the other hand, subtelomeric rearrangements are implicated in a range of disorders, including cancer and intellectual disability. Subtelomeric
research has been slower than that on telomeres due to the challenges posed by the variable nature of the repetitive sequences in this region. Hence, the comprehensive characterisation of subtelomeres is limited to only a few model species; this includes humans, certain yeast, and some parasites.
This thesis explores subtelomere structure and the contribution of subtelomere rearrangements in genome diversification in amniotes, a largely unexplored research area. The thesis Starts with an introduction (Chapter 1), including a literature review highlighting different aspects of the subtelomere, including subtelomere structure, main functions, subtelomere rearrangements and their implications in genomic diversity and diseases. The middle part of the thesis presents three data chapters (Chapters 2, 3 and 4). Chapters 2 and 3 present the cytogenetic approaches, such as karyotype analysis and Fluorescence in situ hybridisation (FISH), which were used to examine the conservation and distribution of chicken subtelomeric genes and repeats in other avian and non-avian reptiles, focusing on Australian species, including seven bird species and three reptile species (Chapters 2 and 3). Chapter 4 presents bioinformatic approaches that were used to characterise the subtelomere in the Tasmanian devil chromosomes, covering GC content, repeats, transposable elements, Interstitial Telomere Sequences (ITS), segmental duplications (SDs) and genes. The final section of this thesis (Chapter 5) presents a general discussion and conclusion.
The data from this thesis not only suggest a level of conservation in subtelomere sequences (genes and repeats) across different bird species but also reveal their highly rearranged nature, including translocations, reductions and deletions. The analysis showed little conservation in the sequences between chickens and reptiles, with an absence of the chicken subtelomeric repeats in reptiles, suggesting that these repetitive sequences experienced recent evolutionary developments (Chapters 2 and 3). The characterisation of the Tasmanian devil subtelomeres (Chapter 4) revealed some shared structural similarities with human subtelomeres, including shared families of transposable elements and genes. However, the results indicate that the Tasmanian devil subtelomeres might be longer than humans, have fewer transposable elements than the rest of the genome, and have shorter and fewer ITS and SDs. The data in this chapter also revealed heterogeneity at the end of some Tasmanian devil chromosomes, suggesting a possible involvement of these subtelomeres in regulating the Tasmanian devil's unique telomere and facial tumours.
This work provides a general overview of the subtelomere landscape and its homology across amniotes, and further investigates the role of subtelomere rearrangements in genetic diversity in birds and reptiles. The work in this thesis enhances our understanding of the structure and function of the subtelomeres, setting the stage for further research vital to a comprehensive understanding of subtelomeres' structure and evolution processes and their role in adaptation and speciation. Such research will have significant implications for evolutionary studies, comparative genomic, gene mapping studies and disease-related studies.
| Date of Award | 2024 |
|---|---|
| Original language | English |
| Supervisor | MD Tariq EZAZ (Supervisor), Janine DEAKIN (Supervisor) & Ambi JAYAL (Supervisor) |