Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 86 for “"Mutation rates"”.
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Dynamic Mutation Rates and Extinction in Sexual Organisms
I analyzed the dynamics of the mutation rate in both finite and infinite randomly-mating populations. Germ-line mutator alleles, alleles that increase the genomic mutation rate, frequently occur when mutations alter the structure or regulation of genes involved in DNA repair, a fraction of the …
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Uncovering the variability, regulatory roles and mutation rates of short tandem repeats
… the variability and function of millions of DNA mutations called single nucleotide polymorphisms. Despite this rapid growth in understanding, short tandem repeats (STRs), genomic elements consisting of a repeating pattern of 2-6 bases, have remained poorly understood. Mutating orders of magnitude …
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Bioluminescence-Based High Precision Bacterial Growth Rate Measurements and Their Potential Application in Quantifying Deleterious Effects of High Mutation Rates
<p>The genomic mutation rate of wild-type Escherichia coli is 3E-3 per generation, a value that is shared by many DNA-based microbes and viruses. A majority of clinical isolates of E. coli also have a mutation rate that is close to the wild-type value. These findings raise the possibility that the …
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Mathematical Modeling and Disease Related Applications: A New Method of Estimating Bacterial Mutation Rates, Dynamics of Killer Yeast in a Chemostat, and Other Problems
… we find adaptation, genetic drift, gene flow, mutation, natural selection and speciation. The following thesis explores bacterial mutation rate, mutants, mutators, and how competition acts as a driving force of adaptation.</p> <p>In chapter 1, the system used in reference for mutation is the …
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Mathematical Modeling and Disease Related Applications: A New Method of Estimating Bacterial Mutation Rates, Dynamics of Killer Yeast in a Chemostat, and Other Problems
… we find adaptation, genetic drift, gene flow, mutation, natural selection and speciation. The following thesis explores bacterial mutation rate, mutants, mutators, and how competition acts as a driving force of adaptation.</p> <p>In chapter 1, the system used in reference for mutation is the …
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Determination of Mutation Rates in Bacteriophage T4 by Unneighborly Base Pairs and a Genetic Analysis of the Error-Prone Repair System of Bacteriophage T4
… studies showed that the 2-aminopurine-induced mutation frequency of a particular base pair can be influenced by the base pair adjacent or penultimate to the measure site. This study extends to 0.3 map units (about 20-80 base pairs) the distance at which a single base-pair substitution can exert …
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Evolutionary Instability Of Genomic Mutation Rate In Rapidly Adapting Asexual Mutator Escherichia Coli Populations
Alleles conferring higher mutation rates (mutators) can fix in asexual populations through a process called ‘mutator hitchhiking’. Theory predicts that repeated mutator hitchhiking can occur in an adapting asexual mutator population. I tested this prediction in two settings: a mutL- population …
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Somatic mutagenesis in humans with deficient DNA repair
The accumulation of mutations in normal cells causes the development of cancer and is implicated as a potential mechanism in the physiological process of ageing. In recent years our ability to interrogate the genome of human cancers and the normal tissues from which they arise has expanded greatly. …
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RNA EXPORT FACTOR ELF1 MAINTAINS GENOME STABILITY IN FISSION YEAST
Genome instability, or frequent mutations within a genome, is deleterious and a hallmark of carcinogenesis. Here, I identified that Elf1, a AAA+ family ATPase involved in mRNA nuclear export, prevents genome instability. Upon deletion, elf1Δ cells grow slowly, forming small colonies. Curiously, …
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Sperm sequencing reveals extensive positive selection in the human germline
… of life, cells of the human body accumulate DNA mutations due to damage from intrinsic causes or exposure to mutagens. Mutations that occur in reproductive cell lineages are known as germline mutations and have the potential to be transmitted to offspring. Germline mutations serve as the origin …
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Physiological response to three environmental stressors predicts fitness and genome quality but not base substitution rate in caenorhabditis elegans
<p>"Since DNA mutations occur all the time and may have deleterious effects on fitness (survival and reproduction), organisms expend substantial metabolic resources to find and repair mutations. This metabolic expenditure is termed the cost of fidelity. If an organism is in "poor" condition and …
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Germline mutation in rare disease
Germline mutation is the ultimate source of evolutionary change and disease-causing variants. Understanding the rates and patterns of human mutation can help us learn about their molecular origins, uncover our evolutionary history and improve our ability to identify the genetic causes of human …
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New strategies for in vivo continuous directed evolution
… and largely restricted to E. coli. Furthermore, mutation rates are limited by the lack of simple mutagenesis methods that can focus mutations to desired portions of a viral genome. In this thesis, I describe the development of several new continuous in vivo directed evolution strategies and tools …
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Inference on a genetic model
… deals with statistical inference on the mutation rates α₁ and α₂ of a population genetic model introduced by Moran [Proc. Camb. Phil. Soc. 54 (1958), pp. 60-71]. The deductive theory by approximate methods of such models has reached an advanced stage but little has been done along the …
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The Tradeoffs for a Viral Mutant with Enhanced Replication Speed
… heterogeneous populations due to high mutation rates and many of these mutations reduce fitness and/or replication speed. However, it is unknown whether mutations can increase replication speed of a virus already well adapted to replication in cultured cells. By sequentially passaging …
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Steady states in rapidly evolving populations
Populations are subject to mutations conferring beneficial effects, as well as mutations conferring deleterious effects. Even if deleterious mutations occur much more frequently than beneficial mutations, the contribution of deleterious mutations to the overall rate of change of the population-wide …
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Multi-resolution modeling of a discrete stochastic process identifies causes of cancer
Detection of cancer-causing mutations within the vast and mostly unexplored human genome is a major challenge. Doing so requires modeling the background mutation rate, a highly non-stationary stochastic process, across regions of interest varying in size from one to millions of positions. Here, we …
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Genome Variation Across Cancers Scales With Tissue Stiffness--An Invasion-Mutation Mechanism
… lung and skin, exhibit more than 30-fold higher mutation rates than those arising in soft tissues, like marrow and brain. This scaling relationship suggests a possible mechanical source of cancerous mutations. We hypothesize that when cancer cells squeeze through small holes in stiff fibrous …
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Safeguarding the mitochondrial genome: identifying components of the mtDNA repair machinery
… are crucial for limiting the accumulation of mutations associated with mitochondrial dysfunction and age-related diseases. Despite this, the pathways responsible for repairing double-strand breaks (DSBs) in animal mitochondria remain poorly characterised. This thesis explores mtDNA repair …
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