ArticleScience advances2023
Epistasis between promoter activity and coding mutations shapes gene evolvability.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- The shape of fitness functions and the distribution of mutational effect sizes jointly limit adaptation by regulatory mutations.Nature ecology & evolution · 2026Article
- Pooled CRISPRi screening reveals fungal-specific drug target candidates.Nature microbiology · 2026Article
- Molecular evolution in light of regulatory-coding epistasis.EMBO reports · 2026Review
- Article
- Predicting antifolate resistance in the unculturable fungal pathogen Pneumocystis jirovecii.PLoS genetics · 2026Article
- The genetic basis of mimicry in the snowy bumble bee (Bombus niveatus) in Anatolia with insights from a color polymorphic gynandromorph.PLoS genetics · 2026Article
- A cost-effective and scalable barcoded library construction method for deep mutational scanning studies.PLoS biology · 2026Article
- Pooled CRISPRi screening reveals fungal-specific vulnerabilities across environments and genetic backgrounds.bioRxiv : the preprint server for biology · 2026Article
- Epistatic drift in protein evolution.Current opinion in genetics & development · 2025Review
- Unraveling Epistatic Interactions Between Sites Under Drug-Dependent Selection in the Mycobacterium tuberculosis Genome.Molecular biology and evolution · 2025Article
- Saturation mapping of MUTYH variant effects using DNA repair reporters.American journal of human genetics · 2025Article
- Cryptic genetic variation shapes the fate of gene duplicates in a protein interaction network.Nature communications · 2025Article
- Considerations in the search for epistasis.Genome biology · 2024Review
- Most azole resistance mutations in the Candida albicans drug target confer cross-resistance without intrinsic fitness cost.Nature microbiology · 2024Article
- Functional Optimization in Distinct Tissues and Conditions Constrains the Rate of Protein Evolution.Molecular biology and evolution · 2024Article
- Contributions of Hyperactive Mutations in MACS infectious diseases · 2024Article
- Cryptic genetic variation shapes the fate of gene duplicates in a protein interaction network.bioRxiv : the preprint server for biology · 2024Article
- A mutational atlas for Parkin proteostasis.Nature communications · 2024Article
- Design and deep learning of synthetic B-cell-specific promoters.Nucleic acids research · 2023Article
- Intra-Frontiers in genetics · 2023Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The evolution of protein-coding genes proceeds as mutations act on two main dimensions: regulation of transcription level and the coding sequence. The extent and impact of the connection between these two dimensions are largely unknown because they have generally been studied independently. By measuring the fitness effects of all possible mutations on a protein complex at various levels of promoter activity, we show that promoter activity at the optimal level for the wild-type protein masks the effects of both deleterious and beneficial coding mutations. Mutations that are deleterious at low activity but masked at optimal activity are slightly destabilizing for individual subunits and binding interfaces. Coding mutations that increase protein abundance are beneficial at low expression but could potentially incur a cost at high promoter activity. We thereby demonstrate that promoter activity in interaction with protein properties can dictate which coding mutations are beneficial, neutral, or deleterious.
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