A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae
- University of Washington, United States
Abstract
Although studies of Saccharomyces cerevisiae have provided many insights into mutagenesis and DNA repair, most of this work has focused on a few laboratory strains. Much less is known about the phenotypic effects of natural variation within S. cerevisiae's DNA repair pathways. Here, we use natural polymorphisms to detect historical mutation spectrum differences among several wild and domesticated S. cerevisiae strains. To determine whether these differences are likely caused by genetic mutation rate modifiers, we use a modified fluctuation assay with a CAN1 reporter to measure de novo mutation rates and spectra in 16 of the analyzed strains. We measure a 10-fold range of mutation rates and identify two strains with distinctive mutation spectra. These strains, known as AEQ and AAR, come from the panel's 'Mosaic beer' clade and share an enrichment for C>A mutations that is also observed in rare variation segregating throughout the genomes of several Mosaic beer and Mixed origin strains. Both AEQ and AAR are haploid derivatives of the diploid natural isolate CBS 1782, whose rare polymorphisms are enriched for C>A as well, suggesting that the underlying mutator allele is likely active in nature. We use a plasmid complementation test to show that AAR and AEQ share a mutator allele in the DNA repair gene OGG1, which excises 8-oxoguanine lesions that can cause C>A mutations if left unrepaired.
Data availability
Sequencing data have been uploaded to the SRA and approved (Accession numbers PRJNA691686).
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Genome evolution across 1,011 Saccharomyces cerevisiae isolates1002 Yeast Genomes Website.
Article and author information
Author details
Funding
National Institute of General Medical Sciences (1R35GM133428-01)
- Kelley Harris
National Institute of General Medical Sciences (P41GM103533)
- Maitreya J Dunham
National Institute of General Medical Sciences (R01GM118854)
- Alan J Herr
Burroughs Wellcome Fund (Career Award at the Scientific Interface)
- Kelley Harris
Kinship Foundation (Searle Scholarship)
- Kelley Harris
Pew Charitable Trusts (Pew Scholarship)
- Kelley Harris
Alfred P. Sloan Foundation (Sloan Fellowship)
- Kelley Harris
National Human Genome Research Institute (T32HG00035)
- Anja R Ollodart
Howard Hughes Medical Institute (Faculty Scholar Award)
- Maitreya J Dunham
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Magnus Nordborg, Austrian Academy of Sciences, Austria
Version history
- Preprint posted: January 11, 2021 (view preprint)
- Received: March 11, 2021
- Accepted: September 14, 2021
- Accepted Manuscript published: September 15, 2021 (version 1)
- Version of Record published: October 7, 2021 (version 2)
- Version of Record updated: December 16, 2021 (version 3)
- Version of Record updated: December 24, 2021 (version 4)
Copyright
© 2021, Jiang 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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A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae
eLife 10:e68285.
https://doi.org/10.7554/eLife.68285
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