A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae

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 p...

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Autores principales:	Pengyao Jiang, Anja R Ollodart, Vidha Sudhesh, Alan J Herr, Maitreya J Dunham, Kelley Harris
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	mutation rate mutation spectrum Saccharomyces cerevisiae mutator phenotype genetic variation reporter assay Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c7105fd1b6ec43f595ed2466e85f39a3
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spelling	oai:doaj.org-article:c7105fd1b6ec43f595ed2466e85f39a32021-11-25T10:26:22ZA modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae10.7554/eLife.682852050-084Xe68285https://doaj.org/article/c7105fd1b6ec43f595ed2466e85f39a32021-09-01T00:00:00Zhttps://elifesciences.org/articles/68285https://doaj.org/toc/2050-084XAlthough 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.Pengyao JiangAnja R OllodartVidha SudheshAlan J HerrMaitreya J DunhamKelley HarriseLife Sciences Publications Ltdarticlemutation ratemutation spectrumSaccharomyces cerevisiaemutator phenotypegenetic variationreporter assayMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mutation rate mutation spectrum Saccharomyces cerevisiae mutator phenotype genetic variation reporter assay Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	mutation rate mutation spectrum Saccharomyces cerevisiae mutator phenotype genetic variation reporter assay Medicine R Science Q Biology (General) QH301-705.5 Pengyao Jiang Anja R Ollodart Vidha Sudhesh Alan J Herr Maitreya J Dunham Kelley Harris A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae
description	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.
format	article
author	Pengyao Jiang Anja R Ollodart Vidha Sudhesh Alan J Herr Maitreya J Dunham Kelley Harris
author_facet	Pengyao Jiang Anja R Ollodart Vidha Sudhesh Alan J Herr Maitreya J Dunham Kelley Harris
author_sort	Pengyao Jiang
title	A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae
title_short	A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae
title_full	A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae
title_fullStr	A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae
title_full_unstemmed	A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae
title_sort	modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within saccharomyces cerevisiae
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/c7105fd1b6ec43f595ed2466e85f39a3
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A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae

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