Comprehensive fitness maps of Hsp90 show widespread environmental dependence
- University of Massachusetts Medical School, United States
- 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.
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Comprehensive fitness maps of Hsp90 show widespread environmental dependenceNCBI Short Read Archive, PRJNA593726.
Article and author information
Author details
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
- Christian R Landry, Université Laval, Canada
Version history
- Received: November 21, 2019
- Accepted: March 3, 2020
- Accepted Manuscript published: March 4, 2020 (version 1)
- 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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Comprehensive fitness maps of Hsp90 show widespread environmental dependence
eLife 9:e53810.
https://doi.org/10.7554/eLife.53810
Further reading
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The emergence of new protein functions is crucial for the evolution of organisms. This process has been extensively researched for soluble enzymes, but it is largely unexplored for membrane transporters, even though the ability to acquire new nutrients from a changing environment requires evolvability of transport functions. Here, we demonstrate the importance of environmental pressure in obtaining a new activity or altering a promiscuous activity in members of the amino acid-polyamine-organocation (APC)-type yeast amino acid transporters family. We identify APC members that have broader substrate spectra than previously described. Using in vivo experimental evolution, we evolve two of these transporter genes, AGP1 and PUT4, toward new substrate specificities. Single mutations on these transporters are found to be sufficient for expanding the substrate range of the proteins, while retaining the capacity to transport all original substrates. Nonetheless, each adaptive mutation comes with a distinct effect on the fitness for each of the original substrates, illustrating a trade-off between the ancestral and evolved functions. Collectively, our findings reveal how substrate-adaptive mutations in membrane transporters contribute to fitness and provide insights into how organisms can use transporter evolution to explore new ecological niches.
