ArticleGenome biology and evolution2011
Protein structural modularity and robustness are associated with evolvability.
Article in Genome biology and evolution, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Selection for Molecularly Complementary Modules (MCMs) Drives the Origins and Evolution of Pleiofunctional, Epistatic Interactomes (PEIs).Life (Basel, Switzerland) · 2026Review
- Conserved structural topologies in RNase A-like and trypsin-like serine proteases: a sequence-based folding analysis.BMC molecular and cell biology · 2025Article
- Experimental recombining of repetitive motifs leads to large functional metallothioneins and demonstrates their modular evolvability potential.Protein science : a publication of the Protein Society · 2025Article
- Article
- Ongoing shuffling of protein fragments diversifies core viral functions linked to interactions with bacterial hosts.Nature communications · 2023Article
- The Modular Architecture of Metallothioneins Facilitates Domain Rearrangements and Contributes to Their Evolvability in Metal-Accumulating Mollusks.International journal of molecular sciences · 2022Article
- Linking protein structural and functional change to mutation using amino acid networks.PloS one · 2022Article
- Switching an active site helix in dihydrofolate reductase reveals limits to subdomain modularity.Biophysical journal · 2021Article
- Chimeric dihydrofolate reductases display properties of modularity and biophysical diversity.Protein science : a publication of the Protein Society · 2019Article
- On the role of sparseness in the evolution of modularity in gene regulatory networks.PLoS computational biology · 2018Article
- Article
- Iron-Sulfur Cluster Biogenesis Chaperones: Evidence for Emergence of Mutational Robustness of a Highly Specific Protein-Protein Interaction.Molecular biology and evolution · 2016Article
- Transhydrogenase promotes the robustness and evolvability of E. coli deficient in NADPH production.PLoS genetics · 2015Article
- Biophysics of protein evolution and evolutionary protein biophysics.Journal of the Royal Society, Interface · 2014Article
- Sequence analysis on the information of folding initiation segments in ferredoxin-like fold proteins.BMC structural biology · 2014Article
- Enzyme recruitment and its role in metabolic expansion.Biochemistry · 2014Review
- The relationship between modularity and robustness in signalling networks.Journal of the Royal Society, Interface · 2013Article
- Defining structural and evolutionary modules in proteins: a community detection approach to explore sub-domain architecture.BMC structural biology · 2013Article
- Intramolecular arrangement of sensor and regulator overcomes relaxed specificity in hybrid two-component systems.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
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2 authors.
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Abstract
Theory suggests that biological modularity and robustness allow for maintenance of fitness under mutational change, and when this change is adaptive, for evolvability. Empirical demonstrations that these traits promote evolvability in nature remain scant however. This is in part because modularity, robustness, and evolvability are difficult to define and measure in real biological systems. Here, we address whether structural modularity and/or robustness confer evolvability at the level of proteins by looking for associations between indices of protein structural modularity, structural robustness, and evolvability. We propose a novel index for protein structural modularity: the number of regular secondary structure elements (helices and strands) divided by the number of residues in the structure. We index protein evolvability as the proportion of sites with evidence of being under positive selection multiplied by the average rate of adaptive evolution at these sites, and we measure this as an average over a phylogeny of 25 mammalian species. We use contact density as an index of protein designability, and thus, structural robustness. We find that protein evolvability is positively associated with structural modularity as well as structural robustness and that the effect of structural modularity on evolvability is independent of the structural robustness index. We interpret these associations to be the result of reduced constraints on amino acid substitutions in highly modular and robust protein structures, which results in faster adaptation through natural selection.
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