University of Massachusetts Medical School Faculty Publications

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Department of Biochemistry and Molecular Pharmacology; Graduate School of Biomedical Sciences

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Article Preprint


Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Ecology and Evolutionary Biology


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 budding yeast with all 44,604 single codon changes encoding 14,160 amino acid variants in Hsp90 and quantified growth effects under standard laboratory conditions and under five stress conditions (elevated temperature, nitrogen starvation, elevated salinity, high ethanol concentration, and oxidative stress caused by diamide). To our knowledge these are the largest comprehensive fitness maps of point mutant growth effects that have been determined. The growth effects of many variants differed between each of the conditions, indicating that environmental conditions can have a large impact on the evolution of Hsp90. Multiple variants provided growth advantages relative to wildtype Hsp90 under individual conditions, however these variants tended to exhibit growth defects in other environments. The diversity of Hsp90 sequences observed in extant eukaryotes preferentially contain amino acid variants that supported robust growth under all tested conditions. Thus, 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.


Evolutionary Biology, Hsp90, deep mutational scanning, yeast, environment, comprehensive fitness maps

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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.

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bioRxiv 823468; doi: Link to preprint on bioRxiv service.

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Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.



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