ArticleProceedings of the National Academy of Sciences of the United States of America2023
Marginal specificity in protein interactions constrains evolution of a paralogous family.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- SamT, a novel peptide modulator of a two-component system revealed by the specific activation of a small RNA in Enterobacteriaceae.Nucleic acids research · 2026Article
- Evolutionary causes and consequences of gene duplication.Nature reviews. Genetics · 2026Review
- Biophysical trade-offs in antibody evolution are resolved by conformation-mediated epistasis.bioRxiv : the preprint server for biology · 2026Article
- Transcription Factor Promiscuity Drives Regulatory Rewiring and Evolvability in Gene Networks in Bacteria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Engineered kin recognition specificities in the TraA cell surface receptor.The ISME journal · 2026Article
- Multiple input-multiple output (MIMO) designs in two-component signalling systems of Mycobacterium tuberculosis.FEMS microbiology reviews · 2026Review
- Design of Specific Peptide Inhibitors of Toxin-Antitoxin-Mediated Antiphage Defense.ACS synthetic biology · 2025Article
- Emergence of antiphage functions from random sequence libraries reveals mechanisms of gene birth.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- High-throughput amino acid-level characterization of the interactions of plasminogen activator inhibitor-1 with variably divergent proteases.Protein science : a publication of the Protein Society · 2025Article
- Symmetry facilitated the evolution of heterospecificity and high-order stoichiometry in vertebrate hemoglobin.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Symmetry facilitated the evolution of heterospecificity and high-order stoichiometry in vertebrate hemoglobin.bioRxiv : the preprint server for biology · 2024Article
- Intrinsic Disorder and Other Malleable Arsenals of Evolved Protein Multifunctionality.Journal of molecular evolution · 2024Review
- Constitutive activation of two-component systems reveals regulatory network interactions in Streptococcus agalactiae.Nature communications · 2024Article
- The genetic architecture of protein interaction affinity and specificity.Nature communications · 2024Article
- Predicting the involvement of polyQ- and polyA in protein-protein interactions by their amino acid context.Heliyon · 2024Article
- Elaboration of the Homer1 recognition landscape reveals incomplete divergence of paralogous EVH1 domains.Protein science : a publication of the Protein Society · 2024Article
- Following the Evolutionary Paths of Dscam1 Proteins toward Highly Specific Homophilic Interactions.Molecular biology and evolution · 2024Article
- Elaboration of the Homer1 Recognition Landscape Reveals Incomplete Divergence of Paralogous EVH1 Domains.bioRxiv : the preprint server for biology · 2024Article
- Conserved patterns of sequence diversification provide insight into the evolution of two-component systems inMicrobial genomics · 2024Article
- Evolutionary history of the cytochrome P450s from Colletotrichum species and prediction of their putative functional roles during host-pathogen interactions.BMC genomics · 2024Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The evolution of novel functions in biology relies heavily on gene duplication and divergence, creating large paralogous protein families. Selective pressure to avoid detrimental cross-talk often results in paralogs that exhibit exquisite specificity for their interaction partners. But how robust or sensitive is this specificity to mutation? Here, using deep mutational scanning, we demonstrate that a paralogous family of bacterial signaling proteins exhibits marginal specificity, such that many individual substitutions give rise to substantial cross-talk between normally insulated pathways. Our results indicate that sequence space is locally crowded despite overall sparseness, and we provide evidence that this crowding has constrained the evolution of bacterial signaling proteins. These findings underscore how evolution selects for "good enough" rather than optimized phenotypes, leading to restrictions on the subsequent evolution of paralogs.
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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.