Biology subjects

Sane, M.

Publications and source records attributed to Sane, M..

5 recordsLinked to original sources

bioRxiv2025

Mutation bias is a key predictor of adaptation rate

A growing body of work indicates that mutation bias -- whereby some types of mutations occur more often than others -- can influence the genetic basis of adaptation and the distribution of fitness effects of new mutations, with potentially important evolutionary consequences. Specifically, reversing an ancestral mutation bias (e.g., in Escherichia coli, shifting from a transition-biased to a transversion-biased mutation spectrum) enhances access to under-sampled variants, increasing the supply of beneficial mutations. However, the effect of mutation bias relative to other factors influencing adaptation remains unclear. By experimentally evolving wild type and mutator E. coli strains in different growth media, we show that mutation bias reversal facilitates early adaptation, altering the genetic basis of adaptation and the type of mutations accumulated under selection. Together, mutation bias, mutation rate, and initial fitness correctly predicted relative adaptation rates for any pair of strains. Our results highlight multiple ways in which mutational processes can shape genetic and phenotypic outcomes of adaptation.

evolutionary biology↗

bioRxiv2024

Mutation bias alters the distribution of fitness effects of mutations

Mutation bias is an important factor determining the diversity of genetic variants available for selection. As adaptation proceeds and some beneficial mutations are fixed, new beneficial mutations become rare, limiting further adaptation. The depletion of beneficial mutations is especially stark within the mutational class favoured by the existing mutation bias. Recent theoretical work predicts that this problem may be alleviated by a change in the direction of mutation bias (i.e., a bias reversal). If populations sample previously underexplored types of mutations, the distribution of fitness effects (DFE) of mutations should shift towards more beneficial mutations. Here, we test this prediction using Escherichia coli, which has a transition mutation bias, with [~]54% single-nucleotide mutations being transitions compared to the unbiased expectation of [~]33% transitions. We generated mutant strains with a wide range of mutation biases, from 97% transitions to 98% transversions, either reinforcing or reversing the wild type transition bias. Quantifying DFEs of [~]100 single mutations obtained from mutation accumulation experiments for each strain, we find strong support for the theoretical prediction. Strains that oppose the ancestral bias (i.e., with a strong transversion bias) have DFEs with the highest proportion of beneficial mutations, whereas strains that exacerbate the ancestral transition bias have up to 10-fold fewer beneficial mutations. Such dramatic differences in the DFE should drive large variation in the rate and outcome of adaptation, suggesting an important and generalized evolutionary role for mutation bias shifts.

evolutionary biology↗

bioRxiv2023

Mutational signatures in wild type Escherichia coli strains reveal dominance of DNA polymerase errors

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.

evolutionary biology↗

bioRxiv2020

Shifts in mutation spectra enhance access to beneficial mutations

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 under-sampled 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 favoured. 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. SIGNIFICANCE STATEMENTMutations are important because they provide raw material for evolution. Some types of mutations occur more often than others, and the strength of such mutational bias varies across species. It is not clear how this variation arises. We experimentally measured the immediate effects of changing the mutation bias of E. coli, and used simulations to understand the long-term effects. Altering mutational bias is beneficial whenever the new bias increases sampling of mutational classes that were previously under-sampled. We also show that historically, bacteria have often experienced such beneficial bias switches. Our work thus demonstrates the importance of mutational biases in evolution. By allowing exploration of new mutational space, altered mutation biases could drive rapid adaptation.

evolutionary biology↗

bioRxiv2018

Antagonistic pleiotropy is unexpectedly rare in new mutations

Pleiotropic effects of mutations may 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. The rare empirical tests of these assumptions have largely focused on beneficial mutations observed under strong selection, whereas most mutations are actually deleterious or neutral, and are removed by selection. 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, which is lower than expected given the distributions of fitness effects for each resource. In some environments, AP was more common in large-effect mutations (but not synergistic pleiotropy, SP); whereas pleiotropic effect sizes were positively correlated for SP (but not AP). Thus, AP is generally rare, 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 is unlikely to cause maladaptive tradeoffs.

evolutionary biology↗