Comprehensive fitness maps of Hsp90 show widespread environmental dependence.

ELife
Julia M FlynnDaniel N A Bolon

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.

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Citations

Aug 8, 2020·Biomolecules·Amanda B AbildgaardRasmus Hartmann-Petersen
Sep 2, 2020·Molecular Biology and Evolution·Pamela A Cote-HammarlofDaniel N A Bolon
Feb 24, 2021·Proceedings of the National Academy of Sciences of the United States of America·Jianzhi Zhang, Haiqing Xu
May 1, 2021·Biology Methods and Protocols·Shreya RouthRiddhiman Dhar
Apr 20, 2021·Computational and Structural Biotechnology Journal·Federico Scossa, Alisdair R Fernie
May 7, 2021·Molecular Ecology·Emma L BerdanInês Fragata
Jul 3, 2021·American Journal of Human Genetics·Jochen WeileFrederick P Roth

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Methods Mentioned

BETA
protein folding
environmental stresses
environmental stress
Illumina sequencing
salt stress
Protein Assay
PCR
restriction digest

Software Mentioned

EMPIRIC
ConSurf
Pymol
PoPMuSic

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