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dc.contributor.authorFlynn, Julia M
dc.contributor.authorRossouw, Ammeret
dc.contributor.authorCote-Hammarlof, Pamela A.
dc.contributor.authorFragata, Ines
dc.contributor.authorMavor, David
dc.contributor.authorHollins, Carl III
dc.contributor.authorBank, Claudia
dc.contributor.authorBolon, Daniel N A
dc.date2022-08-11T08:08:24.000
dc.date.accessioned2022-08-23T15:53:47Z
dc.date.available2022-08-23T15:53:47Z
dc.date.issued2019-12-09
dc.date.submitted2019-11-27
dc.identifier.citation<p>bioRxiv 823468; doi: https://doi.org/10.1101/823468. <a href="https://doi.org/10.1101/823468" target="_blank">Link to preprint on bioRxiv service.</a></p>
dc.identifier.doi10.1101/823468
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29421
dc.description.abstractGene-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.
dc.language.isoen_US
dc.relationNow published in eLife doi: 10.7554/eLife.53810
dc.rightsThe copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectEvolutionary Biology
dc.subjectHsp90
dc.subjectdeep mutational scanning
dc.subjectyeast
dc.subjectenvironment
dc.subjectcomprehensive fitness maps
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectEcology and Evolutionary Biology
dc.titleInvestigating the influence of environment on the evolution of Hsp90 using comprehensive fitness maps [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2657&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1649
dc.identifier.contextkey15882038
refterms.dateFOA2022-08-23T15:53:47Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathfaculty_pubs/1649
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology


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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.
Except where otherwise noted, this item's license is described as 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.