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

eLife

Vidha Sudhesh¹  Pengyao Jiang²  Alan J Herr²  Anja R Ollodart²  Kelley Harris²  Maitreya J Dunham³ 

[1] Molecular and Cellular Biology Program, University of Washington, Seattle, United States;Department of Genome Sciences, University of Washington, Seattle, United States;Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States;

关键词: mutation rate;    mutation spectrum;    Saccharomyces cerevisiae;    mutator phenotype;    genetic variation;    reporter assay;   

DOI  :  10.7554/eLife.68285

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown