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

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.

Metrics

  • 2,323
    Page views
  • 315
    Downloads
  • 18
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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
(2020)
Comprehensive fitness maps of Hsp90 show widespread environmental dependence
eLife 9:e53810.
https://doi.org/10.7554/eLife.53810

Further reading

    1. Evolutionary Biology
    2. Genetics and Genomics
    Tianzhu Xiong et al.
    Research Article Updated

    Hybridization is a major evolutionary force that can erode genetic differentiation between species, whereas reproductive isolation maintains such differentiation. In studying a hybrid zone between the swallowtail butterflies Papilio syfanius and Papilio maackii (Lepidoptera: Papilionidae), we made the unexpected discovery that genomic substitution rates are unequal between the parental species. This phenomenon creates a novel process in hybridization, where genomic regions most affected by gene flow evolve at similar rates between species, while genomic regions with strong reproductive isolation evolve at species-specific rates. Thus, hybridization mixes evolutionary rates in a way similar to its effect on genetic ancestry. Using coalescent theory, we show that the rate-mixing process provides distinct information about levels of gene flow across different parts of genomes, and the degree of rate-mixing can be predicted quantitatively from relative sequence divergence (FST) between the hybridizing species at equilibrium. Overall, we demonstrate that reproductive isolation maintains not only genomic differentiation, but also the rate at which differentiation accumulates. Thus, asymmetric rates of evolution provide an additional signature of loci involved in reproductive isolation.

    1. Developmental Biology
    2. Evolutionary Biology
    Katelyn Mika et al.
    Research Advance

    Structural and physiological changes in the female reproductive system underlie the origins of pregnancy in multiple vertebrate lineages. In mammals, the glandular portion of the lower reproductive tract has transformed into a structure specialized for supporting fetal development. These specializations range from relatively simple maternal nutrient provisioning in egg-laying monotremes to an elaborate suite of traits that support intimate maternal-fetal interactions in Eutherians. Among these traits are the maternal decidua and fetal component of the placenta, but there is considerable uncertainty about how these structures evolved. Previously we showed that changes in uterine gene expression contributes to several evolutionary innovations during the origins of pregnancy (Marinic, Mika, and Lynch 2021). Here we reconstruct the evolution of entire transcriptomes ('ancestral transcriptome reconstruction') and show that maternal gene expression profiles are correlated with degree of placental invasion. These results indicate that an epitheliochorial-like placenta evolved early in the mammalian stem-lineage and that the ancestor of Eutherians had a hemochorial placenta, and suggest maternal control of placental invasiveness. These data resolve major transitions in the evolution of pregnancy and indicate that ancestral transcriptome reconstruction can be used to study the function of ancestral cell, tissue, and organ systems.