The DOI matches its Crossref record; 72 of the 73 references it cites were found in a registry or an index.
Evolutionary Innovations and the Organization of Protein Functions in Genotype Space
Open accessAbstract
The organization of protein structures in protein genotype space is well studied. The same does not hold for protein functions, whose organization is important to understand how novel protein functions can arise through blind evolutionary searches of sequence space. In systems other than proteins, two organizational features of genotype space facilitate phenotypic innovation. The first is that genotypes with the same phenotype form vast and connected genotype networks. The second is that different neighborhoods in this space contain different novel phenotypes. We here characterize the organization of enzymatic functions in protein genotype space, using a data set of more than 30,000 proteins with known structure and function. We show that different neighborhoods of genotype space contain proteins with very different functions. This property both facilitates evolutionary innovation through exploration of a genotype network, and it constrains the evolution of novel phenotypes. The phenotypic diversity of different neighborhoods is caused by the fact that some functions can be carried out by multiple structures. We show that the space of protein functions is not homogeneous, and different genotype neighborhoods tend to contain a different spectrum of functions, whose diversity increases with increasing distance of these neighborhoods in sequence space. Whether a protein with a given function can evolve specific new functions is thus determined by the protein's location in sequence space.
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“The authors estimated a probability of 1 in 10 11 to find an ATP binding protein, suggesting a higher probability than found by Axe.”
From Using statistical methods to model the fine-tuning of molecular machines and systems (2020) · cites this paper as Ferrada and Wagner, 2010
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Currin, A., Swainston, N., Day, P. J., & Kell, D. B. (2014) · Chemical Society Reviews · doi:10.1039/c4cs00351a · Cited by 393
The molecular origins of evolutionary innovations
Wagner, A. (2011) · Trends in Genetics · doi:10.1016/j.tig.2011.06.002 · Cited by 127
Self-citationStructural properties of genotype–phenotype maps
Ahnert, S. E. (2017) · Journal of The Royal Society Interface · doi:10.1098/rsif.2017.0275 · Cited by 110
Schaper, S., & Louis, A. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086635 · Cited by 90
Manrubia, S., Cuesta, J. A., Aguirre, J., Ahnert, S. E., Altenberg, L., Cano, A. V., Catalán, P., Diaz-Uriarte, R., Elena, S. F., García-Martín, J. A., et al. (2021) · Physics of Life Reviews · doi:10.1016/j.plrev.2021.03.004 · Cited by 88
Metadata
- Authors
- Ferrada, E., & Wagner, A.
- Affiliations
- SIB Swiss Institute of Bioinformatics (CH)
- Corresponding author
- Ferrada, Evandro
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-11-30
- Volume
- 5
- Issue
- 11
- Pages
- e14172
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2994758
- OpenAlex
- W2082738116
- Cited by
- 51
- References
- 73
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 4 · 2021: 6 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 7 · 2015: 2 · 2014: 6 · 2013: 2 · 2012: 4
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (315200, 315230, 119697, 129708, 116814)
- Universität Zürich
- SystemsX.ch
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- protein function evolution, genotype space, sequence spaces, enzyme function, protein structure-function relationship, genotype networks, phenotypic innovation, functional diversity
- MeSH terms
- Algorithms, Binding Sites, Enzymes, Genotype, Proteins, Substrate Specificity, Protein Structure, Tertiary, Evolution, Molecular, Databases, Protein, Biocatalysis
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