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Title:Experimental and theoretical investigations of the relationship between fitness and mutation rate evolution in E. coli
Author(s):Sherer, Nicholas
Director of Research:Kuhlman, Thomas E.
Doctoral Committee Chair(s):O'Dwyer, James P.
Doctoral Committee Member(s):Goldenfeld, Nigel D.; Selvin, Paul R.
Department / Program:Physics
Degree Granting Institution:University of Illinois at Urbana-Champaign
Mutation rate
Mismatch Repair
E. coli
Abstract:Mutations are the heritable changes in DNA which make evolution possible. Natural selection acts on the changes in phenotype caused by changes in genotype, and neutral mutations which aren't directly selected on lead to phenomena like genetic drift. The rate at which mutations occur affects how quickly organisms evolve in a phenotypic sense and how quickly their DNA changes at the molecular level, so understanding the mutation rate is important to understanding both selection and neutral phenomena. In the first chapter, we review past work on the evolution of the mutation rate and systems for preventing mutations like the mismatch repair system. In the second chapter, we investigate the mismatch repair system of the model organism Escherichia coli. Mismatch repair systems are found in all organisms. Most mutation are deleterious to an organisms survival, and mismatch repair systems evolved to reduce the frequency of mutations. We have engineered a strain of E. coli where we control the level of expression of some mismatch repair proteins and translationally fused them to fluorescent proteins. This allows us to measure the mutation rate as a function of mismatch repair protein concentration. We find that overexpression of mismatch repair proteins compared to the wildtype does not further reduce the mutation rate in our laboratory environment. In the third chapter, we use the fact that by controlling the level of mismatch repair we can control the mutation rate to investigate the effects of the mutation rate on evolution in a fixed environment. We evolve our E. coli with a controllable mutation rate at five different mutation rates in rich medium at 30° C in 48-well plates in a platereader for 350 generations. There are nine replicates per mutation rate. Each day we measure the growth curve of all replicates at all five mutation rates. We find that the growth curves each day change the soonest at the highest mutation rates and that the replicates' growth curves diverge from each other as the number of generations increases. We find that changes occur predominantly in the lag and stationary phases of growth and not in exponential phase growth. In the fourth chapter, we model the long term evolution of fitness and the mutation rate in an asexual population using numerical simulations and analytic methods. We find a regime of mutation rate evolution with dynamics somewhat resembling those of models of fitness evolution where selection occurs much faster than mutation. We call this the mutator-antimutator sweep regime. In this regime, we are able to summarize the stochastic evolution of the fitness and mutation rate distribution in two dimensions with a Markov process where where the state of the population is captured by the mode of this distribution and transitions between states occur with fixed probabilities. We find inequalities allowing us to separate different regimes of mutation rate evolution, the drift-barrier regime, the mutator-antimutator sweep regime, and the traveling wave regime.
Issue Date:2019-10-07
Rights Information:Copyright 2019 Nicholas Sherer
Date Available in IDEALS:2020-03-02
Date Deposited:2019-12

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