ArticleeLife2021
Contingency and chance erase necessity in the experimental evolution of ancestral proteins.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- The adaptive landscapes of three globaleLife · 2026Article
- Evolutionary causes and consequences of gene duplication.Nature reviews. Genetics · 2026Review
- Free energy perturbations in enzyme kinetic models reveal cryptic epistasis.PLoS computational biology · 2026Article
- Deep models of protein evolution in time generate realistic evolutionary trajectories and functional proteins.bioRxiv : the preprint server for biology · 2026Article
- Historical contingency limits adaptive diversification in a spatially structured environment.Evolution letters · 2026Article
- Epistatic drift in protein evolution.Current opinion in genetics & development · 2025Review
- Stochastic Character Mapping: An Under-Exploited Approach to the Study of Molecular Evolution.Journal of molecular evolution · 2025Article
- PANCS-Binders: a rapid, high-throughput binder discovery platform.Nature methods · 2025Article
- Multiple transitions to high l-DOPA 4,5-dioxygenase activity reveal molecular pathways to convergent betalain pigmentation in Caryophyllales.The New phytologist · 2025Article
- Genes Encoding Intracellular Signaling Proteins in Animals Originated Along with Metazoa and Chordata: Chance or Necessity?Genome biology and evolution · 2025Article
- Transcriptomic Data Reveal Divergent Paths of Chitinase Evolution Underlying Dietary Convergence in Anteaters and Pangolins.Genome biology and evolution · 2025Article
- Protein Quality Control is a Master Modulator of Molecular Evolution in Bacteria.Genome biology and evolution · 2025Review
- High-throughput protein binder discovery by rapid in vivo selection.bioRxiv : the preprint server for biology · 2025Article
- Functional differences between rodent and human PD-1 linked to evolutionary divergence.Science immunology · 2025Article
- Specialization Restricts the Evolutionary Paths Available to Yeast Sugar Transporters.Molecular biology and evolution · 2024Article
- Understanding epistatic networks in the B1 β-lactamases through coevolutionary statistical modeling and deep mutational scanning.Nature communications · 2024Article
- Specialization restricts the evolutionary paths available to yeast sugar transporters.bioRxiv : the preprint server for biology · 2024Article
- Evolution of a plant growth-regulatory protein interaction specificity.Nature plants · 2023Article
- Multifractal foundations of biomarker discovery for heart disease and stroke.Scientific reports · 2023Article
- Virus-assisted directed evolution of biomolecules.Current opinion in chemical biology · 2023Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The roles of chance, contingency, and necessity in evolution are unresolved because they have never been assessed in a single system or on timescales relevant to historical evolution. We combined ancestral protein reconstruction and a new continuous evolution technology to mutate and select proteins in the B-cell lymphoma-2 (BCL-2) family to acquire protein-protein interaction specificities that occurred during animal evolution. By replicating evolutionary trajectories from multiple ancestral proteins, we found that contingency generated over long historical timescales steadily erased necessity and overwhelmed chance as the primary cause of acquired sequence variation; trajectories launched from phylogenetically distant proteins yielded virtually no common mutations, even under strong and identical selection pressures. Chance arose because many sets of mutations could alter specificity at any timepoint; contingency arose because historical substitutions changed these sets. Our results suggest that patterns of variation in BCL-2 sequences - and likely other proteins, too - are idiosyncratic products of a particular and unpredictable course of historical events.
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Registered trials
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