Adaptation in protein fitness landscapes is facilitated by indirect paths
The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph in...
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| Format: | Online |
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eLife Sciences Publications, Ltd
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985287/ |
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pubmed-49852872016-08-23 Adaptation in protein fitness landscapes is facilitated by indirect paths Wu, Nicholas C Dai, Lei Olson, C Anders Lloyd-Smith, James O Sun, Ren Genomics and Evolutionary Biology The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two amino acids at each site. In reality, the dimensionality of protein sequence space is higher (20L) and there may be higher-order interactions among more than two sites. Here we experimentally characterized the fitness landscape of four sites in protein GB1, containing 204 = 160,000 variants. We found that while reciprocal sign epistasis blocked many direct paths of adaptation, such evolutionary traps could be circumvented by indirect paths through genotype space involving gain and subsequent loss of mutations. These indirect paths alleviate the constraint on adaptive protein evolution, suggesting that the heretofore neglected dimensions of sequence space may change our views on how proteins evolve. eLife Sciences Publications, Ltd 2016-07-08 /pmc/articles/PMC4985287/ /pubmed/27391790 http://dx.doi.org/10.7554/eLife.16965 Text en © 2016, Wu et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Wu, Nicholas C Dai, Lei Olson, C Anders Lloyd-Smith, James O Sun, Ren |
| spellingShingle |
Wu, Nicholas C Dai, Lei Olson, C Anders Lloyd-Smith, James O Sun, Ren Adaptation in protein fitness landscapes is facilitated by indirect paths |
| author_facet |
Wu, Nicholas C Dai, Lei Olson, C Anders Lloyd-Smith, James O Sun, Ren |
| author_sort |
Wu, Nicholas C |
| title |
Adaptation in protein fitness landscapes is facilitated by indirect paths |
| title_short |
Adaptation in protein fitness landscapes is facilitated by indirect paths |
| title_full |
Adaptation in protein fitness landscapes is facilitated by indirect paths |
| title_fullStr |
Adaptation in protein fitness landscapes is facilitated by indirect paths |
| title_full_unstemmed |
Adaptation in protein fitness landscapes is facilitated by indirect paths |
| title_sort |
adaptation in protein fitness landscapes is facilitated by indirect paths |
| description |
The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two amino acids at each site. In reality, the dimensionality of protein sequence space is higher (20L) and there may be higher-order interactions among more than two sites. Here we experimentally characterized the fitness landscape of four sites in protein GB1, containing 204 = 160,000 variants. We found that while reciprocal sign epistasis blocked many direct paths of adaptation, such evolutionary traps could be circumvented by indirect paths through genotype space involving gain and subsequent loss of mutations. These indirect paths alleviate the constraint on adaptive protein evolution, suggesting that the heretofore neglected dimensions of sequence space may change our views on how proteins evolve. |
| publisher |
eLife Sciences Publications, Ltd |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985287/ |
| _version_ |
1613627588688740352 |