UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Publication Date
2021-01-23
Document Type
Article
Disciplines
Ecology and Evolutionary Biology | Genetics and Genomics | Molecular Biology
Abstract
The distribution of fitness effects (DFEs) of new mutations across different environments quantifies the potential for adaptation in a given environment and its cost in others. So far, results regarding the cost of adaptation across environments have been mixed, and most studies have sampled random mutations across different genes. Here, we quantify systematically how costs of adaptation vary along a large stretch of protein sequence by studying the distribution of fitness effects of the same approximately 2,300 amino-acid changing mutations obtained from deep mutational scanning of 119 amino acids in the middle domain of the heat shock protein Hsp90 in five environments. This region is known to be important for client binding, stabilization of the Hsp90 dimer, stabilization of the N-terminal-Middle and Middle-C-terminal interdomains, and regulation of ATPase-chaperone activity. Interestingly, we find that fitness correlates well across diverse stressful environments, with the exception of one environment, diamide. Consistent with this result, we find little cost of adaptation; on average only one in seven beneficial mutations is deleterious in another environment. We identify a hotspot of beneficial mutations in a region of the protein that is located within an allosteric center. The identified protein regions that are enriched in beneficial, deleterious, and costly mutations coincide with residues that are involved in the stabilization of Hsp90 interdomains and stabilization of client-binding interfaces, or residues that are involved in ATPase-chaperone activity of Hsp90. Thus, our study yields information regarding the role and adaptive potential of a protein sequence that complements and extends known structural information.
Keywords
adaptation, chaperone, deep mutational scanning, fitness effects, mutations
Rights and Permissions
Copyright © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
DOI of Published Version
10.1093/molbev/msaa211
Source
Cote-Hammarlof PA, Fragata I, Flynn J, Mavor D, Zeldovich KB, Bank C, Bolon DNA. The Adaptive Potential of the Middle Domain of Yeast Hsp90. Mol Biol Evol. 2021 Jan 23;38(2):368-379. doi: 10.1093/molbev/msaa211. PMID: 32871012; PMCID: PMC7826181. Link to article on publisher's site
Journal/Book/Conference Title
Molecular biology and evolution
Related Resources
PubMed ID
32871012
Repository Citation
Cote-Hammarlof PA, Fragata I, Flynn JM, Mavor D, Zeldovich KB, Bank C, Bolon DN. (2021). The Adaptive Potential of the Middle Domain of Yeast Hsp90. Open Access Publications by UMMS Authors. https://doi.org/10.1093/molbev/msaa211. Retrieved from https://escholarship.umassmed.edu/oapubs/4556
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Included in
Ecology and Evolutionary Biology Commons, Genetics and Genomics Commons, Molecular Biology Commons