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Title: The influence of general and inducible hypermutation on adaptation during experimental evolution
Creator: Weigand, Michael R.
Date: 2011
Collection: Electronic Theses & Dissertations
Description: 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: Novel studies of spontaneous mutation : measurements of fitness in the field and gene expression in the lab
Creator: Roles, Angela Jennifer
Date: 2007
Collection: Electronic Theses & Dissertations

Title: The effects of caffeine on the UV-induced frequency of mutations in Chinese hamster fibroblasts
Creator: Philipps, Constance
Date: 1976
Collection: Electronic Theses & Dissertations

Title: On the evolution of mutation bias in digital organisms
Creator: Rupp, Matthew
Date: 2011
Collection: Electronic Theses & Dissertations
Description: 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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Title: Detection of boscalid resistance and the H272R mutation in the SDHB gene of Blumeriella jaapii
Creator: Outwater, Cory Alan
Date: 2014
Collection: Electronic Theses & Dissertations
Description: Cherry leaf spot (CLS), caused by the fungus Blumeriella jaapii, is a major disease of tart cherry (Prunus cerasus) trees, leading to early defoliation which results in poor fruit quality, reduced fruit set, and tree death. Pristine, a commonly-utilized fungicide for CLS management in Michigan, is a premix of boscalid, a succinate dehydrogenase inhibitor, and pyraclostrobin, a quinone outside inhibitor. Reduced efficacy of Pristine for CLS control observed in...
Show moreCherry leaf spot (CLS), caused by the fungus Blumeriella jaapii, is a major disease of tart cherry (Prunus cerasus) trees, leading to early defoliation which results in poor fruit quality, reduced fruit set, and tree death. Pristine, a commonly-utilized fungicide for CLS management in Michigan, is a premix of boscalid, a succinate dehydrogenase inhibitor, and pyraclostrobin, a quinone outside inhibitor. Reduced efficacy of Pristine for CLS control observed in field trials and commercial orchards highlighted the importance of resistance monitoring. A total of 1,288 isolates from commercial orchards and 111 isolates from non-treated trees were collected in 2010 and 2011 and assayed on boscalid-amended media at concentrations of 0, 0.1, 0.5, 1, 2.5, 5, 10, and 25 g ml-1. The minimum inhibitory concentration (MIC) of boscalid was determined after incubation at 23 oC for 14 days. Isolates from non-treated trees had MIC values ranging from 0.1 to 0.5 μg ml-1 while isolates from commercial orchards ranged from 0.1 to > 25 μg ml-1 . Isolates with MIC values of > 25 μg ml-1 were considered resistant and comprised 22% and 35% of isolates in 2010 and 2011 respectively. Sequencing of the SDHB gene of resistant isolates led to the detection of the amino acid mutation H272R known to confer boscalid resistance. The occurrence of the H272R mutation in Michigan populations of B. jaapii is correlated with the reduction in sensitivity to boscalid observed in commercial orchards.
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Title: Bloom syndrome as a human mutator mutation
Creator: Warren, Stephen Theodore
Date: 1981
Collection: Electronic Theses & Dissertations

Title: Adaptation and specialization in biological and digital organisms
Creator: Ostrowski, Elizabeth Anne
Date: 2005
Collection: Electronic Theses & Dissertations

Title: The development of a sensitive human epithelial cell assay for environmental mutagens
Creator: Jou, Yuh-Shan
Date: 1991
Collection: Electronic Theses & Dissertations

Title: Functional analysis of cytoplasmic [gamma]-actin mutations causing non-syndromic, progressive autosomal dominant hearing loss
Creator: Korrapati, Soumya
Date: 2009
Collection: Electronic Theses & Dissertations

Title: Isolation and characterization of symbiotically defective mutant strains of Rhizobium trifolii and Rhizobium meliloti
Creator: Gardiol, Alicia E.
Date: 1985
Collection: Electronic Theses & Dissertations

Title: Population growth, dynamics and evolution in Escherichia coli : theoretical and experimental studies
Creator: Attar, Farida Vasi
Date: 2000
Collection: Electronic Theses & Dissertations

Title: Evidence from mutation spectra that the UV hypermutability of xeroderma pigmentosum variant cells reflects abnormal, error-prone replication on a template containing photoproducts
Creator: Wang, Yi-Ching
Date: 1993
Collection: Electronic Theses & Dissertations

Title: On the beneficial effects of deleterious mutations
Creator: Covert, Arthur W.
Date: 2010
Collection: Electronic Theses & Dissertations

Title: Understanding the role of standing genetic variation in functional genetics and compensatory evolution
Creator: Chari, Sudarshan R.
Date: 2014
Collection: Electronic Theses & Dissertations
Description: 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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Title: Evolution of laboratory and natural populations of Escherichia coli
Creator: Maddamsetti, Rohan
Date: 2016
Collection: Electronic Theses & Dissertations
Description: My dissertation spans two dichotomies: evolution in the laboratory versus evolution in nature, and asexual versus sexual evolutionary dynamics. In Chapter 1 I describe asexual evolutionary dynamics in one population of Lenski’s long-term evolution experiment with Escherichia coli. I describe cohorts of mutations that sweep to fixation together as characteristic of clonal interference dynamics. I also describe an ecological interaction that evolved and then went extinct after thousands of...
Show moreMy dissertation spans two dichotomies: evolution in the laboratory versus evolution in nature, and asexual versus sexual evolutionary dynamics. In Chapter 1 I describe asexual evolutionary dynamics in one population of Lenski’s long-term evolution experiment with Escherichia coli. I describe cohorts of mutations that sweep to fixation together as characteristic of clonal interference dynamics. I also describe an ecological interaction that evolved and then went extinct after thousands of generations, and discuss how such interactions affect cohorts of mutations. In Chapter 2 I report that conserved core genes tend to be targets of selection in the long-term experiment. In Chapter 3, I investigate the surprising observation that synonymous genetic diversity is not uniform across the genomes of natural E. coli isolates. This observation is surprising because in clonal organisms with a constant point mutation rate, synonymous diversity should be constant across the genome. I use patterns of synonymous mutations in the long-term experiment to argue that genome-wide variation in the mutation rate does not adequately explain patterns of synonymous genetic diversity. In Chapter 4, I propose that recombination and gene flow could account for genome-wide variation in synonymous genetic diversity. In Chapter 5, I analyze E. coli genomes isolated from an evolution experiment with recombination in which E. coli K-12 with known growth defects could donate genetic material to recipient populations founded by long-term experiment clones. The degree of recombination varied dramatically across sequenced clones. The strongest predictor of successful transfer was proximity to the oriT origin of transfer in the K-12 donors. Donor alleles close to oriT replaced their recipient counterparts at a high rate, and in many of those cases, known beneficial mutations in the recipients were replaced by donor alleles.
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Title: Mechanisms of adaptation and speciation : an experimental study using artificial life
Creator: Anderson, Carlos Jesus
Date: 2013
Collection: Electronic Theses & Dissertations
Description: Detailed experimental studies in evolutionary biology are sometimes difficult--even with model organisms. Theoretical models alleviate some of these difficulties and often provide clean results, but they cannot always capture the complexity of dynamic evolutionary processes. Artificial life systems are tools that fall somewhere between model organisms and theoretical models that have been successfully used to study evolutionary biology. These systems simulate simple organisms that replicate,...
Show moreDetailed experimental studies in evolutionary biology are sometimes difficult--even with model organisms. Theoretical models alleviate some of these difficulties and often provide clean results, but they cannot always capture the complexity of dynamic evolutionary processes. Artificial life systems are tools that fall somewhere between model organisms and theoretical models that have been successfully used to study evolutionary biology. These systems simulate simple organisms that replicate, acquire random mutations, and reproduce differentially; as a consequence, they evolve naturally (i.e., evolution itself is not simulated). Here I use the software Avida to study several open questions on the genetic mechanisms of adaptation and speciation.In Chapter 1 (p. 13), I investigated whether beneficial alleles during adaptation came from new mutations or standing genetic variation--alleles already present in the population. I found that most beneficial alleles came from standing genetic variation, but new mutations were necessary for long-term evolution. I also found that adaptation from standing genetic variation was faster than from new mutations. Finally, I found that recombination brought together beneficial combinations of alleles from standing genetic variation.In Chapter 2 (p. 31), I investigated the probability of compensatory adaptation vs. reversion. Compensatory adaptation is the fixation of mutations that ameliorate the effects of deleterious mutations while the original deleterious mutations remain fixed. I found that compensatory adaptation was very common, but the window of opportunity for reversion was increased when the initial fitness of the population was high, the population size was large, and the mutation rate was high. The reason that the window of opportunity for reversion was constrained was that negative epistatic interactions with compensatory mutations prevented the revertant from being beneficial to the population.In Chapter 3 (p. 58), I showed experimentally that compensatory adaptation can lead to reproductive isolation (specifically, postzygotic isolation). In addition, I found that the strength of this isolation was independent of the effect size of the original deleterious mutations. Finally, I found that both deleterious and compensatory mutations contribute equally to reproductive isolation.Reproductive isolation between populations often evolves as a byproduct of independent adaptation to new environments, but the selective pressures of these environments may be divergent (`ecological speciation') or uniform (`mutation-order speciation'). In Chapter 4 (p. 75), I compared directly the strength of postzygotic isolation generated by ecological and mutation-order processes with and without migration. I found that ecological speciation generally formed stronger isolation than mutation-order speciation and that mutation-order speciation was more sensitive to migration than ecological speciation.Under the Dobzhansky-Muller model of speciation, hybrid inviability or sterility results from the evolution of genetic incompatibilities (DMIs) between species-specific alleles. This model predicts that the number of pairwise DMIs between species should increase quadratically through time, but the few tests of this `snowball effect' have had conflicting results. In Chapter 5 (p. 101), I show that pairwise DMIs accumulated quadratically, supporting the snowball effect. I found that more complex genetic interactions involved alleles that rescued pairwise incompatibilities, explaining the discrepancy between the expected accumulations of DMIs and observation.
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Title: Part I, Studies on the hamster ribonucleotide reductase genes : Part II, Construction of mutations in the chicken adult alpha globin genes
Creator: Bates, Paul F.
Date: 1985
Collection: Electronic Theses & Dissertations

Title: The evolutionary potential of populations on complex fitness landscapes
Creator: Bryson, David Michael
Date: 2012
Collection: Electronic Theses & Dissertations
Description: Evolution is a highly contingent process, where the quality of the solutions produced is affected by many factors. I explore and describe the contributions of three such aspects that influence overall evolutionary potential: the prior history of a population, the type and frequency of mutations that the organisms are subject to, and the composition of the underlying genetic hardware. I have systematically tested changes to a digital evolution system, Avida, measuring evolutionary potential in...
Show moreEvolution is a highly contingent process, where the quality of the solutions produced is affected by many factors. I explore and describe the contributions of three such aspects that influence overall evolutionary potential: the prior history of a population, the type and frequency of mutations that the organisms are subject to, and the composition of the underlying genetic hardware. I have systematically tested changes to a digital evolution system, Avida, measuring evolutionary potential in seven different computational environments ranging in complexity of the underlying fitness landscapes. I have examined trends and general principles that these measurements demonstrate and used my results to optimize the evolutionary potential of the system, broadly enhancing performance. The results of this work show that history and mutation rate play significant roles in evolutionary potential, but the final fitness levels of populations are remarkably stable to substantial changes in the genetic hardware and a broad range of mutation types.
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