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Evolution of Evolvability? Understanding Mutation Rate

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Evolution of Evolvability? Understanding Mutation Rate Evolution of Evolvability? Understanding Mutation Rate Plasticity A thesis submitted to the University of Manchester for the degree of Doctor of Philosophy in the Faculty of Science and Engineering 2018 Huw WE Richards School of Earth and Environmental Sciences Faculty of Science and Engineering Table of Contents i. Abbreviations ……………………………………………………………………………………........... 12 ii. Abstract ………………………………………………………………………………………………………. 13 iii. Declaration …………………………………………………………………………………………………. 14 iv. Acknowledgments ……………………………………………………………………………………... 15 1. Introduction …………………………………………………………………………………………………… 16 1.1. General Introduction …………………………………………………………………………………… 17 1.2. Evolvability …………………………………………………………………………………………………. 18 1.2.1. Robustness ………………………………………………………………………..…………….. 20 1.2.2. Modularity ………………………………………………………………………………….……. 22 1.3. Evolution of Mutation Rates ……………………………………………………………………….. 24 1.3.1. Scaling of Mutation Rates across species …….……………………………………. 24 1.3.2. Selection on the Mutation Rate ……….……….………………………………………. 29 1.3.3. Variation in Mutation Rates ……………………………………………………………… 32 1.3.4. Adaptiveness of Variable Mutation Rates …………………………….…………… 34 1.4. Measuring Mutation Rates ………………………………………………………………………….. 36 1.4.1. Luria-Delbrück Fluctuation assay ………………………………………………………. 36 1.4.2. Mutation Accumulation ………………………………………………..……………….…. 38 1.4.3. Measuring Environmental Dependence of Mutation Rates …………...…. 39 1.4.4. Caveats in using the Fluctuation assay …………………………..……………….… 39 1.5. Mutation Rate Plasticity ……………………………………………………………………………… 40 1.5.1. Stress-Induced Mutagenesis ……………..……………………………………………... 41 1.5.1.1. SOS Response ……………………………………………………………..…….…..44 1.5.1.2. General Stress Response ………………………………………..…………….. 47 1.5.2. Density Associated Mutation Rate Plasticity …………………………………….. 49 1.5.2.1. Quorum Sensing ……………………………………………………………………. 54 1.6. Summary of Thesis ……………………………………………………………………………………… 56 1.6.1. Chapter 2: Spontaneous Mutation Rate is a Plastic Trait Associated with Population Density across Domains of Life ………………………………….……………….. 56 1.6.1.1. Author Contributions ……………………………………………………..…….. 58 1.6.2. Chapter 3: Evolution of Density Associated Mutation Rate Plasticity in two disparate species of Archaea ………………………………………………..……………….. 58 1.6.2.1. Author Contributions ………………………………………………………..….. 59 2 1.6.3. Chapter 4: Evolution of Density Associated Mutation Rate Plasticity in strains of Escherichia coli ……………………………………………………………………………… 59 1.6.3.1. Author Contributions ……………………………………………..…………..… 60 1.6.4. Chapter 5: Highly conserved molecular mechanisms modulate density associated mutation rate plasticity in Escherichia coli ……………………………….…. 60 1.6.4.1. Author Contributions ………..………………………………………………….. 61 1.6.5. Discussion Chapter …………………………………………………………………………… 61 1.6.5.1. Author Contributions …………………………………………………….……… 61 1.7. References ………………………………………………………………………………………………….. 62 2. Spontaneous Mutation Rate is a Plastic Trait Associated with Population Density across Domains of Life ……………………………………………………………………………………. 82 2.1. Abstract ………………………………………………………………………………………………………. 83 2.2. Introduction ………………………………………………………………………………………………… 84 2.3. Results ………………………………………………………………………………………………………… 86 2.4. Discussion …………………………………………………………………………………………………. 102 2.5. Materials and Methods …………………………………………………………………………….. 104 2.5.1. Strains of bacteria and yeast used in Chapter 2…..………..…………… 104 2.5.2. Media ………………………………………………………………………………….….……… 105 2.5.3. Fluctuation tests with bacteria ……………………………………………………….. 106 2.5.4. Fluctuation tests with yeast ……………………………………………………………. 107 2.5.5. Estimation of Mutation Rates …………………………………………………………..108 2.5.6. Statistical Analysis …………………………………………………………………….……. 108 2.5.7. Whole Genome Sequencing ……………………………………………………………. 109 2.5.8. Published mutation rate search criteria ………………………………………….. 111 2.5.9. Phylogeny used in analysing published mutation rates …………………… 116 2.6. References ………………………………………………………………………………………………… 124 2.7. Appendix …………………………………………………………………………………………………… 130 3. Evolution of Density Associated Mutation Rate Plasticity in two disparate species of Archaea ……………………………………………………………………………………………………. 159 3.1. Abstract …………………………………………………………………………………………………….. 160 3.2. Introduction ……………………………………………………………………………………………… 161 3.3. Materials and Methods …………………………………………………………………………….. 164 3.3.1 Strains used in this study ………………………………………………………………… 164 3 3.3.2 Media …………………………………………………………………………………………….. 164 3.3.3 Fluctuation tests in Archaea …………………………………………………………… 165 3.3.4 Estimation of Mutation Rates …………………………………………………………. 166 3.3.5 BLAST Analysis of Archaeal genetic and protein sequences ………..…… 167 3.3.6 Statistical Analysis …………………………………………………………………………... 168 3.4 Results ………………………………………………………………………………………………..……… 169 3.4.1 DAMP in the Archaea ………………………………………………………………..……. 169 3.4.2 BLAST analysis of Archaeal nucleotide and amino acid sequences ….. 171 3.5 Discussion ……………………………………………………………………………………..…………... 173 3.6 References …………………………………………………………………………………..…………….. 177 3.7 Appendix ……………………………………………………………………………………..…………….. 181 3.7.1 Alignments from the BLASTp analysis ……………………………..………………. 181 3.7.1.1 Amino Acid Sequence alignment of Escherichia coli MutT to Sulfolobus acidocaldarius DSM 639 ………………………..………………… 181 3.7.1.2 Amino Acid Sequence alignment of Saccharomyces cerevisiae PCD1 to Haloferax volcanii DS2 …………………………………………………..…..… 182 3.7.1.3 Amino Acid Sequence alignment of Escherichia coli MutT to Haloferax volcanii DS2 ………………………………………………………..……. 182 3.7.2 Media Preparation for both Archaea species …………………………….……. 183 3.7.2.1 Sulfolobus acidocaldarius media ………………………………………..…….. 183 3.7.2.2 Haloferax volcanii media …………………………………………..……………… 185 3.7.3 Statistical model outputs ………………………………………………………………… 188 3.7.3.1 Model output for Figure 3.1A ……………………………….………………….. 188 3.7.3.2 Model output for Figure 3.1B …………………………………………………… 188 3.7.3.3 Model output for Figure 3.2 …………………………………………………….. 188 4. Evolution of Density Associated Mutation Rate Plasticity within strains of Escherichia coli ……………………………………………………………………………………………… 189 4.1. Abstract …………………………………………………………………………………………………….. 190 4.2. Introduction .…………………………………………………………………………………………….. 191 4.3. Materials and Methods …………………………………………………………………………….. 158 4.3.1. Strains used in this study ………………………………..………………………………. 194 4.3.2. Media ………………………………………………………………………….…….……..……. 194 4.3.3. Fluctuation tests ………………….…………………………………………….………..…. 194 4 4.3.3.1. Variation of mutation rate and DAMP in strains of E. coli ….… 194 4.3.3.2. Interaction between SIM and DAMP in strains of E. coli ……... 196 4.3.4. Estimation of mutation rates ………………………………..….…………………….. 197 4.3.5. ECOR phylogeny ………………………………………………………………………….….. 198 4.3.6. Phylogenetic analysis ………………………………………………….……………..…... 198 4.3.7. Statistical analysis ……………………………………………………….………………….. 201 4.4. Results ………………………………………………………………………………………………………. 202 4.4.1. Mutation rates and DAMP in ECOR collection ……………….…………….…. 202 4.4.1.1. Variation in both average mutation rate and DAMP in ECOR collection .………………………………………………………………………………. 202 4.4.1.2. Variation in average mutation rate and DAMP robust to fitness effects of resistance mutation ………………………………..……………… 206 4.4.1.3. Fitness effects of resistance mutation …………..……………………….. 210 4.4.1.4. Variation in average mutation rate and DAMP with weighted median estimate of fitness effects …………………………………..…….. 212 4.4.2. Phylogenetic analysis of average mutation rate and DAMP in ECOR collection ………………………………………………………………..……………………. 214 4.4.3. Interplay between SIM and DAMP in two isolates of E. coli …….……. 219 4.5. Discussion …………………………………………………………………………………………………..221 4.6. References ………………………………………………………………………………………………… 227 4.7. Appendix …………………………………………………………………………………………………… 231 4.7.1. Statistical model outputs …………………………….……………….…………………. 231 4.7.1.1. Model output for Figure 4.2A ……………………………………………… 231 4.7.1.2. Model output for Figure 4.3A ……………………………………………… 235 4.7.1.3. Model output for Figure 4.4A ……………………………………………… 240 4.7.1.4. Model output for Figure 4.5A ……………………………………………... 245 4.7.1.5. Model output for Figure 4.8 ……………………………………………….. 249 4.7.2. Diagnostic plots of BayesTraits Analysis …………………………………………. 254 4.7.2.1. Diagnostic plots for analysis of average mutation rate not co- estimating fitness effects of the resistance mutation …………….. 254 4.7.2.2. Diagnostic plots for degree of DAMP not co-estimating fitness effects of the resistance mutation …………………………………………. 256 5 4.7.2.3. Diagnostic plots for analysis of average mutation rate co- estimating fitness effects of the resistance mutation …………….. 257 4.7.2.4. Diagnostic plots for degree of DAMP co-estimating fitness effects of the resistance mutation …………………………………………………….. 259 4.7.2.5. Diagnostic plots for analysis of the correlation between the average mutation rate and degree of DAMP when not co- estimating the fitness effect of the resistance mutation ………… 260 4.7.2.6. Diagnostic plots for analysis of the correlation between the average mutation rate and degree of DAMP when not co- estimating the fitness effect of the resistance mutation ………… 262 4.7.3. Strains of bacteria used in Chapter 4 ……..………………………………………. 265 5. Highly conserved molecular mechanisms modulate density associated mutation rate plasticity in Escherichia coli ……………………………………………………………………. 272 5.1. Abstract …………………………………………………………………………………………………….. 273 5.2. Introduction ……………………………………………………………………………………………… 274 5.3. Materials
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