ArticlePloS one2017
Percolation in protein sequence space.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Descent from a common ancestor restricts exploration of protein sequence space.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Ancestral sequences of a large promiscuous enzyme family correspond to bridges in sequence space in a network representation.Journal of the Royal Society, Interface · 2021Article
- The GH19 Engineering Database: Sequence diversity, substrate scope, and evolution in glycoside hydrolase family 19.PloS one · 2021Article
- The scale-free nature of protein sequence space.PloS one · 2018Article
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The currently known protein sequences are not distributed equally in sequence space, but cluster into families. Analyzing the cluster size distribution gives a glimpse of the large and unknown extant protein sequence space, which has been explored during evolution. For six protein superfamilies with different fold and function, the cluster size distributions followed a power law with slopes between 2.4 and 3.3, which represent upper limits to the cluster distribution of extant sequences. The power law distribution of cluster sizes is in accordance with percolation theory and strongly supports connectedness of extant sequence space. Percolation of extant sequence space has three major consequences: (1) It transforms our view of sequence space as a highly connected network where each sequence has multiple neighbors, and each pair of sequences is connected by many different paths. A high degree of connectedness is a necessary condition of efficient evolution, because it overcomes the possible blockage by sign epistasis and reciprocal sign epistasis. (2) The Fisher exponent is an indicator of connectedness and saturation of sequence space of each protein superfamily. (3) All clusters are expected to be connected by extant sequences that become apparent as a higher portion of extant sequence space becomes known. Being linked to biochemically distinct homologous families, bridging sequences are promising enzyme candidates for applications in biotechnology because they are expected to have substrate ambiguity or catalytic promiscuity.
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