Natural variation in the consequences of gene overexpression and its implications for evolutionary trajectories
- University of Wisconsin-Madison, United States
Abstract
Copy number variation (CNV) through gene or chromosome amplification provides a route for rapid phenotypic variation and supports long-term evolution of gene functions. Although the evolutionary importance of CNV is known, little is understood about how genetic background influences CNV tolerance. Here, we measured fitness costs of over 4,000 over-expressed genes in 15 Saccharomyces cerevisiae strains representing different lineages, to explore natural variation in tolerating gene overexpression (OE). Strain-specific effects dominated the fitness costs of gene OE. We report global differences in the consequences of gene OE, independent of the amplified gene, as well as gene-specific effects that were dependent on the genetic background. Natural variation in the response to gene OE could be explained by several models, including strain-specific physiological differences, resource limitations, and regulatory sensitivities. This work provides new insight on how genetic background influences tolerance to gene amplification and the evolutionary trajectories accessible to different backgrounds.
Data availability
Barcode sequencing data are available in the Short Read Archive under accession number GSE171586. RNA-Seq data are available in GEO accession number GSE171585.
Article and author information
Author details
Funding
National Cancer Institute (R01CA229532)
- James Hose
- Adam Jochem
- Audrey P Gasch
U.S. Department of Energy (DE-SC0018409)
- Mike Place
- Audrey P Gasch
National Institutes of Health (GT32GM007133)
- DeElegant Robinson
National Human Genome Research Institute (5T32HG002760)
- DeElegant Robinson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Robinson 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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Natural variation in the consequences of gene overexpression and its
implications for evolutionary trajectories
eLife 10:e70564.
https://doi.org/10.7554/eLife.70564
