Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/79772
Title: DIRECT REPEATS AND DELETIONS IN MITOCHONDRIAL DNA: CASUAL AND EVOLUTIONARY ASPECTS
Authors: LAKSHMI NARAYANAN LAKSHMANAN
Keywords: mitochondrial DNA, deletion mutation, direct repeat, DNA misalignment, evolution, thermodynamics
Issue Date: 27-Dec-2013
Source: LAKSHMI NARAYANAN LAKSHMANAN (2013-12-27). DIRECT REPEATS AND DELETIONS IN MITOCHONDRIAL DNA: CASUAL AND EVOLUTIONARY ASPECTS. ScholarBank@NUS Repository.
Abstract: In this thesis, I employed a computational approach using genome analysis and statistical and thermodynamics-based modeling to understand the role of sequence motifs and DNA misalignments in mitochondrial DNA (mtDNA) deletion mutagenesis. Meta-analysis of age-related deletion breakpoints indicated that in human and rhesus monkey but not in mouse and rat, the average distance observed between a mtDNA breakpoint and its nearest direct repeat (DR) motif was significantly smaller than what was expected by random chance. Comparative analysis of the influence of global and sequence-specific attributes of mtDNA on the total number of DRs revealed that the bias in synonymous codon usage within protein coding genes was the most important determinant of mtDNA DR count. Analysis of deletion breakpoints using a theoretical model based on thermodynamic principles of DNA hybridization indicated that age-related mtDNA deletions in human, rhesus monkey and mouse arose by misalignment-dependent process involving short sequences of 4bp length.
URI: http://scholarbank.nus.edu.sg/handle/10635/79772
Appears in Collections:Ph.D Theses (Open)

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