ArticlePLoS genetics2022
Viral protein instability enhances host-range evolvability.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Narrowed host ranges do not constrain future host range expansion in RNA phage Φ6.Journal of virology · 2026Article
- Quantifying and combating zoonotic viruses poised for emergence: Using multiplex receptor screening and decoy engineering technologies.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Towards accurate artificial intelligence models for strain-level phage-host prediction.Briefings in bioinformatics · 2026Article
- More evolvable bacteriophages better suppress their host.Evolutionary applications · 2024Article
- Viral Receptor-Binding Protein Evolves New Function through Mutations That Cause Trimer Instability and Functional Heterogeneity.Molecular biology and evolution · 2024Article
- Characterization ofFood science & nutrition · 2024Article
- High temperature delays and low temperature accelerates evolution of a new protein phenotype.Nature communications · 2024Article
- Bacteriophage Φ21's receptor-binding protein evolves new functions through destabilizing mutations that generate non-genetic phenotypic heterogeneity.Virus evolution · 2024Article
- Host range expansion of Acinetobacter phage vB_Ab4_Hep4 driven by a spontaneous tail tubular mutation.Frontiers in cellular and infection microbiology · 2024Article
- Viral Evolution Shaped by Host Proteostasis Networks.Annual review of virology · 2023Review
- Comparison of bacterial suppression by phage cocktails, dual-receptor generalists, and coevolutionarily trained phages.Evolutionary applications · 2023Article
- The evolutionary potential of influenza A virus hemagglutinin is highly constrained by epistatic interactions with neuraminidase.Cell host & microbe · 2022Article
- Viral protein instability enhances host-range evolvability.PLoS genetics · 2022Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Viruses are highly evolvable, but what traits endow this property? The high mutation rates of viruses certainly play a role, but factors that act above the genetic code, like protein thermostability, are also expected to contribute. We studied how the thermostability of a model virus, bacteriophage λ, affects its ability to evolve to use a new receptor, a key evolutionary transition that can cause host-range evolution. Using directed evolution and synthetic biology techniques we generated a library of host-recognition protein variants with altered stabilities and then tested their capacity to evolve to use a new receptor. Variants fell within three stability classes: stable, unstable, and catastrophically unstable. The most evolvable were the two unstable variants, whereas seven of eight stable variants were significantly less evolvable, and the two catastrophically unstable variants could not grow. The slowly evolving stable variants were delayed because they required an additional destabilizing mutation. These results are particularly noteworthy because they contradict a widely supported contention that thermostabilizing mutations enhance evolvability of proteins by increasing mutational robustness. Our work suggests that the relationship between thermostability and evolvability is more complex than previously thought, provides evidence for a new molecular model of host-range expansion evolution, and identifies instability as a potential predictor of viral host-range evolution.
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Registered trials
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