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Department of Biochemistry and Molecular Pharmacology

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Amino Acids, Peptides, and Proteins | Ecology and Evolutionary Biology | Fungi | Genetic Phenomena | Genetics and Genomics


Gene-environment interactions have long been theorized to influence molecular evolution. However, the environmental dependence of most mutations remains unknown. Using deep mutational scanning, we engineered yeast with all 44,604 single codon changes encoding 14,160 amino acid variants in Hsp90 and quantified growth effects under standard conditions and under five stress conditions. To our knowledge, these are the largest determined comprehensive fitness maps of point mutants. The growth of many variants differed between conditions, indicating that environment can have a large impact on Hsp90 evolution. Multiple variants provided growth advantages under individual conditions; however, these variants tended to exhibit growth defects in other environments. The diversity of Hsp90 sequences observed in extant eukaryotes preferentially contains variants that supported robust growth under all tested conditions. Rather than favoring substitutions in individual conditions, the long-term selective pressure on Hsp90 may have been that of fluctuating environments, leading to robustness under a variety of conditions.


Hsp90, S. cerevisiae, deep mutational scanning, evolutionary biology, fitness map, genetics, genomics

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Copyright Flynn et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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Flynn JM, Rossouw A, Cote-Hammarlof P, Fragata I, Mavor D, Hollins C 3rd, Bank C, Bolon DN. Comprehensive fitness maps of Hsp90 show widespread environmental dependence. Elife. 2020 Mar 4;9:e53810. doi: 10.7554/eLife.53810. PMID: 32129763; PMCID: PMC7069724. Link to article on publisher's site

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.