{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/106168"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/106168","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Experimental and theoretical investigations of the relationship between fitness and mutation rate evolution in E. coli","abstract":"The student, Nicholas Sherer, accepted the attached license on 2019-10-04 at 14:23.","abstract_html":"The student, Nicholas Sherer, accepted the attached license on 2019-10-04 at 14:23.","abstract_has_math":false,"creators":["Sherer, Nicholas"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Physics","degree_department":null,"school":null,"contributors":["Kuhlman, Thomas E.","O'Dwyer, James P.","Goldenfeld, Nigel D.","Selvin, Paul R."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-03-02T21:58:03Z","date_published":"2020-03-02T21:58:03Z","updated_at":"2026-07-22T22:24:45Z","subjects":["Evolution","Mutation rate","Mismatch Repair","E. coli"],"languages":["en"],"rights":["Copyright 2019 Nicholas Sherer"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/106168","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kuhlman, Thomas E.","O'Dwyer, James P.","Goldenfeld, Nigel D.","Selvin, Paul R."]},{"key":"dc:creator","label":"Author","values":["Sherer, Nicholas"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2020-03-02T21:58:03Z","2019-10-07","2019-12"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Physics"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Evolution","Mutation rate","Mismatch Repair","E. coli"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2019 Nicholas Sherer"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/106168"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The student, Nicholas Sherer, accepted the attached license on 2019-10-04 at 14:23.","The student, Nicholas Sherer, submitted this Dissertation for approval on 2019-10-04 at 14:23.","This Dissertation was approved for publication on 2019-10-07 at 13:35.","DSpace SAF Submission Ingestion Package generated from Vireo submission #14485 on 2020-02-28 at 17:12:43","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.","Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2020-02-28 without embargo terms","Made available in DSpace on 2020-03-02T21:58:03Z (GMT). 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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.","Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2020-02-28 without embargo terms","Made available in DSpace on 2020-03-02T21:58:03Z (GMT). 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