ArticleeLife2019
Molecular function limits divergent protein evolution on planetary timescales.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 42 citations in OpenAlex.
- Gene function predicts divergence across molecular levels.bioRxiv : the preprint server for biology · 2026Article
- Rapidly evolving orphan immunity genes protect human gut bacteria from intoxication by the type VI secretion system.bioRxiv : the preprint server for biology · 2025Article
- A methodology for calculating the rarity of diverse proteins based on functional specificity and thermodynamic stability.PloS one · 2025Article
- Functional Optimization in Distinct Tissues and Conditions Constrains the Rate of Protein Evolution.Molecular biology and evolution · 2024Article
- GENERALIST: A latent space based generative model for protein sequence families.PLoS computational biology · 2023Article
- Domain Architecture Based Methods for Comparative Functional Genomics Toward Therapeutic Drug Target Discovery.Journal of molecular evolution · 2023Review
- In silico analysis decodes transthyretin (TTR) binding and thyroid disrupting effects of per- and polyfluoroalkyl substances (PFAS).Archives of toxicology · 2023Article
- Proteins from ThermophilicACS omega · 2022Article
- Structural bioinformatics enhances the interpretation of somatic mutations in KDM6A found in human cancers.Computational and structural biotechnology journal · 2022Article
- A unified evolutionary origin for the ubiquitous protein transporters SecY and YidC.BMC biology · 2021Article
- In silico and gene expression analysis of the acute inflammatory response of gilthead seabream (Sparus aurata) after subcutaneous administration of carrageenin.Fish physiology and biochemistry · 2021Article
- Systematic dissection of σCell reports · 2021Article
- Universal Constraints on Protein Evolution in the Long-Term Evolution Experiment with Escherichia coli.Genome biology and evolution · 2021Article
- The Relationship between the Misfolding Avoidance Hypothesis and Protein Evolutionary Rates in the Light of Empirical Evidence.Genome biology and evolution · 2021Article
- Poorly Conserved P15 Proteins of Cileviruses Retain Elements of Common Ancestry and Putative Functionality: A Theoretical Assessment on the Evolution of Cilevirus Genomes.Frontiers in plant science · 2021Article
- Evidence for the Rapid and Divergent Evolution of Mycoplasmas: Structural and Phylogenetic Analysis of Enolases.Frontiers in molecular biosciences · 2021Article
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Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Functional conservation is known to constrain protein evolution. Nevertheless, the long-term divergence patterns of proteins maintaining the same molecular function and the possible limits of this divergence have not been explored in detail. We investigate these fundamental questions by characterizing the divergence between ancient protein orthologs with conserved molecular function. Our results demonstrate that the decline of sequence and structural similarities between such orthologs significantly slows down after ~1-2 billion years of independent evolution. As a result, the sequence and structural similarities between ancient orthologs have not substantially decreased for the past billion years. The effective divergence limit (>25% sequence identity) is not primarily due to protein sites universally conserved in all linages. Instead, less than four amino acid types are accepted, on average, per site across orthologous protein sequences. Our analysis also reveals different divergence patterns for protein sites with experimentally determined small and large fitness effects of mutations. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.