@article {140651, title = {Mutational signatures in wild type Escherichia coli strains reveal predominance of DNA polymerase errors.}, journal = {Genome Biol Evol}, year = {2024}, month = {2024 Feb 24}, abstract = {

While mutational processes operating in the Escherichia coli genome have been revealed by multiple laboratory experiments, the contribution of these processes to accumulation of bacterial polymorphism and evolution in natural environments is unknown. To address this question, we reconstruct signatures of distinct mutational processes from experimental data on E. coli hypermutators, and ask how these processes contribute to differences between naturally occurring E. coli strains. We show that both mutations accumulated in the course of evolution of wild type strains in nature and in the lab-grown non-mutator laboratory strains are explained predominantly by the low fidelity of DNA polymerases II and III. By contrast, contributions specific to disruption of DNA repair systems cannot be detected, suggesting that temporary accelerations of mutagenesis associated with such disruptions are unimportant for within-species evolution. These observations demonstrate that accumulation of diversity in bacterial strains in nature is predominantly associated with errors of DNA polymerases.

}, issn = {1759-6653}, doi = {10.1093/gbe/evae035}, author = {Garushyants, Sofya K and Sane, Mrudula and Selifanova, Maria V and Agashe, Deepa and Bazykin, Georgii A and Gelfand, Mikhail S} } @article {134597, title = {Revisiting the Role of Genetic Variation in Adaptation}, journal = {AMERICAN NATURALIST }, year = {2023}, month = {09/2023}, abstract = {

Evolutionary biologists have thought about the role of genetic variation during adaptation for a very long time-before we understood the organization of the genetic code, the provenance of ge-netic variation, and how such variation influenced the phenotypes on which natural selection acts. Half a century after the discovery of the structure of DNA and the unraveling of the genetic code, we have a rich understanding of these problems and the means to both delve deeper and widen our perspective across organisms and natural pop-ulations. The 2022 Vice Presidential Symposium of the American So-ciety of Naturalists highlighted examples of recent insights into the role of genetic variation in adaptive processes, which are compiled in this special section. The work was conducted in different parts of the world, included theoretical and empirical studies with diverse or-ganisms, and addressed distinct aspects of how genetic variation influ-ences adaptation. In our introductory article to the special section, we discuss some important recent insights about the generation and maintenance of genetic variation, its impacts on phenotype and fit-ness, its fate in natural populations, and its role in driving adaptation. By placing the special section articles in the broader context of recent developments, we hope that this overview will also serve as a useful in-troduction to the field.

}, doi = {10.1086/726012}, author = {Agashe, Deepa and Sane, Mrudula and Singhal, Shivansh} } @article {129162, title = {Shifts in mutation spectra enhance access to beneficial mutations.}, journal = {Proc Natl Acad Sci U S A.}, volume = {120}, year = {2023}, month = {05/2023}, pages = {e2207355120}, abstract = {

Biased mutation spectra are pervasive, with wide variation in the magnitude of mutational biases that influence genome evolution and adaptation. How do such diverse biases evolve? Our experiments show that changing the mutation spectrum allows populations to sample previously undersampled mutational space, including beneficial mutations. The resulting shift in the distribution of fitness effects is advantageous: Beneficial mutation supply and beneficial pleiotropy both increase, while deleterious load reduces. More broadly, simulations indicate that reducing or reversing the direction of a long-term bias is always selectively favored. Such changes in mutation bias can occur easily via altered function of DNA repair genes. A phylogenetic analysis shows that these genes are repeatedly gained and lost in bacterial lineages, leading to frequent bias shifts in opposite directions. Thus, shifts in mutation spectra may evolve under selection and can directly alter the outcome of adaptive evolution by facilitating access to beneficial mutations.

}, doi = {10.1073/pnas.2207355120}, author = {Sane, Mrudula and Diwan, Gaurav D and Bhat, BA and Wahl, LM and Agashe, Deepa} } @article {43852, title = {Antagonistic pleiotropy for carbon use is rare in new mutations.}, journal = {Evolution}, year = {2018}, month = {2018 Aug 10}, abstract = {

Pleiotropic effects of mutations underlie diverse biological phenomena such as ageing and specialization. In particular, antagonistic pleiotropy ("AP": when a mutation has opposite fitness effects in different environments) generates tradeoffs, which may constrain adaptation. Models of adaptation typically assume that AP is common - especially among large-effect mutations - and that pleiotropic effect sizes are positively correlated. Empirical tests of these assumptions have focused on de novo beneficial mutations arising under strong selection. However, most mutations are actually deleterious or neutral, and may contribute to standing genetic variation that can subsequently drive adaptation. We quantified the incidence, nature, and effect size of pleiotropy for carbon utilization across 80 single mutations in Escherichia coli that arose under mutation accumulation (i.e., weak selection). Although \~{}46\% of the mutations were pleiotropic, only 11\% showed AP; among beneficial mutations, only \~{}4\% showed AP. In some environments, AP was more common in large-effect mutations; and AP effect sizes across environments were often negatively correlated. Thus, AP for carbon use is generally rare (especially among beneficial mutations); is not consistently enriched in large-effect mutations; and often involves weakly deleterious antagonistic effects. Our unbiased quantification of mutational effects therefore suggests that antagonistic pleiotropy may be unlikely to cause maladaptive tradeoffs.

}, issn = {1558-5646}, doi = {10.1111/evo.13569}, author = {Sane, Mrudula and Miranda, Joshua John and Agashe, Deepa} } @article {3547, title = {Large-Effect Beneficial Synonymous Mutations Mediate Rapid and Parallel Adaptation in a Bacterium.}, journal = {Mol Biol Evol}, year = {2016}, month = {2016 Feb 23}, abstract = {

Contrary to previous understanding, recent evidence indicates that synonymous codon changes may sometimes face strong selection. However, it remains difficult to generalize the nature, strength, and mechanism(s) of such selection. Previously, we showed that synonymous variants of a key enzyme-coding gene (fae) of Methylobacterium extorquens AM1 decreased enzyme production and reduced fitness dramatically. We now show that during laboratory evolution, these variants rapidly regained fitness via parallel yet variant-specific, highly beneficial point mutations in the N-terminal region of fae. These mutations (including four synonymous mutations) had weak but consistently positive impacts on transcript levels, enzyme production, or enzyme activity. However, none of the proposed mechanisms (including internal ribosome pause sites or mRNA structure) predicted the fitness impact of evolved or additional, engineered point mutations. This study shows that synonymous mutations can be fixed through strong positive selection, but the mechanism for their benefit varies depending on the local sequence context.

}, issn = {1537-1719}, doi = {10.1093/molbev/msw035}, author = {Agashe, Deepa and Sane, Mrudula and Phalnikar, Kruttika and Diwan, Gaurav D and Habibullah, Alefiyah and Martinez-Gomez, Norma Cecilia and Sahasrabuddhe, Vinaya and Polachek, William and Wang, Jue and Chubiz, Lon M and Marx, Christopher J} }