1. Evolutionary Biology
  2. Genetics and Genomics
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Comprehensive fitness maps of Hsp90 show widespread environmental dependence

  1. Julia M Flynn
  2. Ammeret Rossouw
  3. Pamela Cote-Hammarlof
  4. Inês Fragata
  5. David Mavor
  6. Carl Hollins
  7. Claudia Bank
  8. Daniel NA Bolon  Is a corresponding author
  1. University of Massachusetts Medical School, United States
  2. Instituto Gulbenkian de Ciência, Portugal
Research Article
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Cite this article as: eLife 2020;9:e53810 doi: 10.7554/eLife.53810

Abstract

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.

Data availability

Next generation sequencing data has been deposited to the NCBI short read archive (Project # PRJNA593726). Tabulated raw counts of all variants in all conditions are included in the manuscript in Figure 1 - source data 1 and Figure 2 - source data 2. Source data files have been provided for Figure 1, 2, 3, 4, 5 and 6.

The following data sets were generated

Article and author information

Author details

  1. Julia M Flynn

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5490-393X
  2. Ammeret Rossouw

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Pamela Cote-Hammarlof

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Inês Fragata

    Instituto Gulbenkian de Ciência, Oeiras, Portugal
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6865-1510
  5. David Mavor

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Carl Hollins

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0410-9639
  7. Claudia Bank

    Instituto Gulbenkian de Ciência, Oeiras, Portugal
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4730-758X
  8. Daniel NA Bolon

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    Dan.Bolon@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5857-6676

Funding

National Institutes of Health (R01-GM112844)

  • Julia M Flynn
  • Ammeret Rossouw
  • Pamela Cote-Hammarlof
  • David Mavor
  • Carl Hollins
  • Daniel NA Bolon

National Institutes of Health (F32-GM119205)

  • Julia M Flynn

Fundação para a Ciência e a Tecnologia (JPIAMR/0001/2016)

  • Inês Fragata

EMBO Installation Grant (IG4152)

  • Claudia Bank

ERC Starting Grant (804569-FIT2GO)

  • Claudia Bank

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Christian R Landry, Université Laval, Canada

Publication history

  1. Received: November 21, 2019
  2. Accepted: March 3, 2020
  3. Accepted Manuscript published: March 4, 2020 (version 1)
  4. Version of Record published: March 13, 2020 (version 2)

Copyright

© 2020, Flynn et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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