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Title
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The influence of general and inducible hypermutation on adaptation during experimental evolution
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Creator
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Weigand, Michael R.
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Date
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2011
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Collection
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Electronic Theses & Dissertations
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Description
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Hypermutator (or mutator) strains of bacteria have been observed in a variety of clinical, environmental, and laboratory populations with up to 1000-fold increases in spontaneous mutation rates. Defects in DNA repair machinery responsible for general hypermutation most commonly include the inactivation of methyl-directed mismatch repair that result in constitutive increases in mutation rate. Alternatively, mutagenic DNA repair only transiently raises mutation rates through the activation of...
Show moreHypermutator (or mutator) strains of bacteria have been observed in a variety of clinical, environmental, and laboratory populations with up to 1000-fold increases in spontaneous mutation rates. Defects in DNA repair machinery responsible for general hypermutation most commonly include the inactivation of methyl-directed mismatch repair that result in constitutive increases in mutation rate. Alternatively, mutagenic DNA repair only transiently raises mutation rates through the activation of low-fidelity polymerases in response to DNA-damaging stress conditions. The widespread existence of both general and inducible mutator genotypes suggests that evolutionary strategies of bacteria include mechanisms for increasing mutability. This work investigates the influence of hypermutation on adaptation through experimental evolution with the contextually relevant model organisms Pseudomonas cichorii 302959 and P. aeruginosa PAO1. Following ~500 generations of growth, both model organisms exhibited comparable improvements in fitness, independent of mutator status, suggesting that hypermutation does not impede adaptation through mutation accumulation. Both general and inducible hypermutation facilitated genotypic diversification that was not observed in non-mutator lineages. The mechanistic differences underlying general and inducible hypermutation were reflected in unique spectra of nucleotide substitutions but did not restrict access to parallel adaptive traits despite considerable variation in gene expression profiles. The diversity in colony morphologies and gene expression traits observed in mutator lineages may represent a broad exploration of sequence space that is no doubt a favorable strategy for adaptation.
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Title
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On the evolution of mutation bias in digital organisms
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Creator
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Rupp, Matthew
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Date
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2011
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Collection
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Electronic Theses & Dissertations
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Description
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Mutation is one of the primary drivers of genetic change. In this work I study mutation biases, which are sets of different genetic-state inflow probabilities. Mutation biases have the potential to change the composition of genomes over time, leading to divergent short- and long-term evolutionary outcomes. I use digital organisms, self-replicating computer programs, to explore whether or not mutation biases are capable of altering the long-term adaptive behavior of populations; whether...
Show moreMutation is one of the primary drivers of genetic change. In this work I study mutation biases, which are sets of different genetic-state inflow probabilities. Mutation biases have the potential to change the composition of genomes over time, leading to divergent short- and long-term evolutionary outcomes. I use digital organisms, self-replicating computer programs, to explore whether or not mutation biases are capable of altering the long-term adaptive behavior of populations; whether mutation biases can be competitive traits; and whether mutation biases can evolve. I find that mutation biases can alter the long-term adaptive behavior of mutation bias-obligate populations in terms of both mean fitness and complex trait evolution. I also find that mutation biases can compete against one another under a variety of conditions, meaning mutation bias can selectable over relatively-short periods of time. The competitive success of a mutation bias does not always depend upon the presence of beneficial mutations, implicating an increase in the probability of neutral mutations as a sufficient mechanism for bias selection. Finally, I demonstrate that by giving organisms a mutable mutation bias allele, populations preferentially evolve to possess specific biases over others. Overall, this work shows that mutation bias can act as a selectable trait, influencing the evolution of populations with regard to both their internal-genetic and external environments.
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