Evidence map›Paper›PMID 32129763›Full record

ArticleeLife2020

Comprehensive fitness maps of Hsp90 show widespread environmental dependence.

Julia M Flynn, Ammeret Rossouw, Pamela Cote-Hammarlof, Inês Fragata, David Mavor, Carl Hollins, Claudia Bank, Daniel Na Bolon

Open access · goldAbstract read
In one paragraph

Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 99 citations in OpenAlex.

  1. Review
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  16. Article
  17. Insights into Hsp90 mechanism andFrontiers in molecular biosciences · 2024
    Review
  18. Article
  19. Article
  20. Emerging maps of allosteric regulation in cellular networks.Current opinion in structural biology · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Julia M FlynnDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.ORCID 0000-0002-5490-393X
Ammeret RossouwDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.
Pamela Cote-HammarlofDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.
Inês FragataInstituto Gulbenkian de Ciência, Oeiras, Portugal.ORCID 0000-0001-6865-1510
David MavorDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.
Carl HollinsDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.ORCID 0000-0003-0410-9639
Claudia BankInstituto Gulbenkian de Ciência, Oeiras, Portugal.ORCID 0000-0003-4730-758X
Daniel Na BolonDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.ORCID 0000-0001-5857-6676
University of Massachusetts Chan Medical School · USInstituto Gulbenkian de Ciência · PT

Funding

Relating protein interaction networks to physiology by systematic mutant analysesR01GM112844 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BOLON, DANIEL N · 2015 to 2023
$2.7M
Probing the mechanism of the Hsp90 chaperone using systematic dominant negative mutational analysesF32GM119205 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI FLYNN, JULIA MARK · 2016 to 2017
$119k
EMBO Installation Grant IG4152ERC Starting Grant 804569-FIT2GOFundação para a Ciência e a Tecnologia JPIAMR/0001/2016NIGMS NIH HHS F32 GM119205NIGMS NIH HHS R01 GM112844
6 · The paper itself

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.

Indexed as

Gene-Environment InteractionAdaptation, PhysiologicalEpistasis, GeneticGene Expression Regulation, FungalGenetic FitnessHSP90 Heat-Shock ProteinsModels, MolecularMutationProtein ConformationSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsStress, PhysiologicalHSP90 Heat-Shock ProteinsSaccharomyces cerevisiae Proteinsdeep mutational scanningevolutionary biologyfitness mapgeneticsgenomicsHsp90S. cerevisiae

Identifiers

PMID32129763
PMCPMC7069724
OpenAlexW3009158419

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.