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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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Mechanisms of adaptation in Oryza and Arabidopsis
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Creator
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Grillo, Michael A.
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Date
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2013
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Collection
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Electronic Theses & Dissertations
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Description
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Here I present a dissertation aimed at understanding the mechanisms of adaptation in two wild rice species and locally adapted populations of Arabidopsis thaliana. First, I assess the genetic architecture of adaptation in the wild progenitors of cultivated rice, by identifying QTL for a number of putative adaptive traits. Through this work flowering time was revealed as a key adaptation for habitat preference between these species. In the next chapter I attempt to elucidate the genetic basis...
Show moreHere I present a dissertation aimed at understanding the mechanisms of adaptation in two wild rice species and locally adapted populations of Arabidopsis thaliana. First, I assess the genetic architecture of adaptation in the wild progenitors of cultivated rice, by identifying QTL for a number of putative adaptive traits. Through this work flowering time was revealed as a key adaptation for habitat preference between these species. In the next chapter I attempt to elucidate the genetic basis of a major flowering time QTL through fine mapping. I continue my examination of flowering time genetics by examining the genetic basis of flowering time differentiation between locally adapted populations of Arabidopsis thaliana. Finally, I conduct a thorough study of comparative floral biology to identify key traits that control mating system divergence between the wild rice relatives. This work sets the stage for future efforts to understand the genetic basis of mating system evolution.
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Title
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Understanding the role of standing genetic variation in functional genetics and compensatory evolution
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Creator
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Chari, Sudarshan R.
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Date
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2014
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Collection
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Electronic Theses & Dissertations
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Description
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Conventionally the phenotypic outcome of a mutation is considered to be due to a specific DNA lesion. But it has long been known that mutational effects can be conditional on environment (GxE) and genetic background (GxG). Thus it is standard practice to perform experiments by controlling for rearing environment and using co-isogenic strains. Though such a controlled approach has been very successful in enabling many discoveries, by not considering conditional effects our understanding of...
Show moreConventionally the phenotypic outcome of a mutation is considered to be due to a specific DNA lesion. But it has long been known that mutational effects can be conditional on environment (GxE) and genetic background (GxG). Thus it is standard practice to perform experiments by controlling for rearing environment and using co-isogenic strains. Though such a controlled approach has been very successful in enabling many discoveries, by not considering conditional effects our understanding of biological systems is incomplete. My research utilized conditionality in terms of genetic background and standing genetic variation therein to understand whether mutational interactions can themselves be background dependent. I demonstrated that a majority of mutational interactions identified via a dominant modifier screen are background dependent. Extending this idea of contingency in terms of standing genetic variation to the phenomenon of compensatory evolution in the presence of deleterious mutations, I demonstrated that natural populations of Drosophila melanogaster possess standing genetic variation for compensatory alleles to ameliorate even severe phenotypic defects. I further demonstrated that, despite considerable standing variation to ameliorate the focal phenotype perturbed by the mutation, natural selection exploits alternative evolutionary trajectories to recover fitness. Additionally this model system also allowed me to understand that loss of sexual signaling can be compensated by modulating behavioural and life history traits.
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