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The mutation rate and mutations' effects on fitness are crucial to evolution. Mutation rates are under selection due to linkage between mutation rate modifiers and mutations' effects on fitness. The linkage between a higher mutation rate and more beneficial mutations selects for higher mutation rates, while the linkage between a higher mutation rate and more deleterious mutations selects for lower mutation rates. The net direction of selection on mutations rates depends on the fitness landscape, and a great deal of work has elucidated the fitness landscapes of mutations. However, tests of the effect of varying a mutation rate on evolution in a single organism in a single environment have been difficult. This has been studied using strains of antimutators and mutators, but these strains may differ in additional ways and typically do not allow for continuous variation of the mutation rate. To help investigate the effects of the mutation rate on evolution, we have genetically engineered a strain of E. coli with a point mutation rate that can be smoothly varied over two orders of magnitude. We did this by engineering a strain with inducible control of the mismatch repair proteins MutH and MutL. We used this strain in an approximately 350 generation evolution experiment with controlled variation of the mutation rate. We confirmed the construct and the mutation rate were stable over this time. Sequencing evolved strains revealed a higher number of single nucleotide polymorphisms at higher mutations rates, likely due to either the beneficial effects of these mutations or their linkage to beneficial mutations.
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Higher-fitness yeast genotypes are less robust to deleterious mutations
Natural selection drives populations toward higher fitness, but second-order selection for adaptability and mutational robustness can also influence evolution. In many microbial systems, diminishing-returns epistasis contributes to a tendency for more-fit genotypes to be less adaptable, but no analogous patterns for robustness are known. To understand how robustness varies across genotypes, we measure the fitness effects of hundreds of individual insertion mutations in a panel of yeast strains. We find that more-fit strains are less robust: They have distributions of fitness effects with lower mean and higher variance. These differences arise because many mutations have more strongly deleterious effects in faster-growing strains. This negative correlation between fitness and robustness implies that second-order selection for robustness will tend to conflict with first-order selection for fitness.
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- Award ID(s):
- 1655960
- PAR ID:
- 10122105
- Publisher / Repository:
- American Association for the Advancement of Science (AAAS)
- Date Published:
- Journal Name:
- Science
- Volume:
- 366
- Issue:
- 6464
- ISSN:
- 0036-8075
- Page Range / eLocation ID:
- p. 490-493
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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