ArticlePLoS genetics2018
Differential strengths of molecular determinants guide environment specific mutational fates.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Effects of Extreme Climatic Events on Evolutionary Processes.Global change biology · 2025Review
- Mitochondrial DNA Genomes Reveal Relaxed Purifying Selection During Human Population Expansion after the Last Glacial Maximum.Molecular biology and evolution · 2024Article
- Protein stability prediction by fine-tuning a protein language model on a mega-scale dataset.PLoS computational biology · 2024Article
- ProteinGym: Large-Scale Benchmarks for Protein Design and Fitness Prediction.bioRxiv : the preprint server for biology · 2023Article
- Distribution of mutation rates challenges evolutionary predictability.Microbiology (Reading, England) · 2023Article
- Article
- Chemical rescue of mutant proteins in living Saccharomyces cerevisiae cells by naturally occurring small molecules.G3 (Bethesda, Md.) · 2021Article
- The adaptive landscape of a metallo-enzyme is shaped by environment-dependent epistasis.Nature communications · 2021Article
- Consequences of mutation accumulation for growth performance are more likely to be resource-dependent at higher temperatures.BMC ecology and evolution · 2021Article
- Fitness effects of spontaneous mutations in a warming world.Evolution; international journal of organic evolution · 2021Article
- Quantifying the Evolutionary Constraints and Potential of Hepatitis C Virus NS5A Protein.mSystems · 2021Article
- Elevated temperature increases genome-wide selection on de novo mutations.Proceedings. Biological sciences · 2021Article
- Recent advances in understanding the role of proteostasis.Faculty reviews · 2021Review
- An experimental test of temperature-dependent selection on mitochondrial haplotypes inEcology and evolution · 2020Article
- Using deep mutational scanning to benchmark variant effect predictors and identify disease mutations.Molecular systems biology · 2020Article
- Distinct metabolic states of a cell guide alternate fates of mutational buffering through altered proteostasis.Nature communications · 2020Article
- Article
- Recent insights into the genotype-phenotype relationship from massively parallel genetic assays.Evolutionary applications · 2019Review
- Chance and pleiotropy dominate genetic diversity in complex bacterial environments.Nature microbiology · 2019Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Organisms maintain competitive fitness in the face of environmental challenges through molecular evolution. However, it remains largely unknown how different biophysical factors constrain molecular evolution in a given environment. Here, using deep mutational scanning, we quantified empirical fitness of >2000 single site mutants of the Gentamicin-resistant gene (GmR) in Escherichia coli, in a representative set of physical (non-native temperatures) and chemical (small molecule supplements) environments. From this, we could infer how different biophysical parameters of the mutations constrain molecular function in different environments. We find ligand binding, and protein stability to be the best predictors of mutants' fitness, but their relative predictive power differs across environments. While protein folding emerges as the strongest predictor at minimal antibiotic concentration, ligand binding becomes a stronger predictor of mutant fitness at higher concentration. Remarkably, strengths of environment-specific selection pressures were largely predictable from the degree of mutational perturbation of protein folding and ligand binding. By identifying structural constraints that act as determinants of fitness, our study thus provides coarse mechanistic insights into the environment specific accessibility of mutational fates.
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