The time-dependence of molecular evolution, specifically over short timescales, has been shown to be a major confounding factor in the analysis of nucleotide changes between closely related strains or species. The assumption that selection works extremely quickly to purge all of the deleterious changes is at odds with the Nearly Neutral model of evolution, whereby the majority of changes are only mildly deleterious and therefore impose only a minor fitness cost so they are relatively rapidly purged only in populations with large effective population sizes.The aim of this project was to explore the patterns of nucleotide changes evident between the core genomes of nine E. coli and Shigella strains, with the latter having adopted a specific ecological niche in the recent evolutionary past. The Shigellae and E. coli show little difference in their extant genome compositions, in terms of nucleotide composition and genome size, however there are a markedly higher number of pseudogenes and insertion sequences present in the Shigella genomes.The polymorphism profiles of the core genomes reveal a time-dependency of dN/dS, Ti/Tv, +AT/+GC and the Metabolic cost of Amino acid changes, the nucleotide data showing a clear separation of the E. coli from the Shigellae, with the latter showing trends indicative of weaker purifying selection. Additionally these differences are evident when examining the nucleotide ratios (+AT/+GC & Ti/Tv) along the core genome, also revealing patterns of evolution associated with genome position. A simulation based approach reveals different projected nucleotide contents for the E. coli and Shigellae genomes further highlighting their different evolutionary paths as evident from the polymorphism profiles.The methods employed and developed in this study provide a useful and effective toolset for examining the evolution of bacterial genomes over short timescales, especially in light of the availability of multiple whole genome sequences for a given ‘species’.
|Date of Award||1 Jul 2009|
|Supervisor||Edward Feil (Supervisor)|