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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: 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: 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: 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: 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: 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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Title: Characterization of ultraviolet light-induced diphtheria toxin-resistant mutations in normal and xeroderma pigmentosum human fibroblasts
Creator: Glover, Thomas Warren
Date: 1979
Collection: Electronic Theses & Dissertations

Title: Glucocorticoid receptor gene mutations associate with glucocorticoid-responsive leukocyte and production traits in cattle
Creator: Jacob, Jennifer Brigitte
Date: 2003
Collection: Electronic Theses & Dissertations

Title: Mechanisms of adaptation in Oryza and Arabidopsis
Creator: Grillo, Michael A.
Date: 2013
Collection: Electronic Theses & Dissertations
Description: 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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