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

Citation

Jiang, Pengyao et al. (2021), A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae, Dryad, Dataset, https://doi.org/10.5061/dryad.ht76hdrhh

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.

Methods

This includes some large files generated during data analysis process for the paper. 

- sites from S.paradoxus that have been aligned to S.cerevisiae: Scer_para_consol_SNPs.txt

- vcf file for the 1011 S.cerevisiae after filtering to count mutation spectra from polymorphisms: 

1011_SNP_bi_mm0.8_GT_u_rm_final_no_close.vcf.gz

Funding

National Institute of General Medical Sciences, Award: 1R35GM133428-01

National Institute of General Medical Sciences, Award: P41GM103533

National Institute of General Medical Sciences, Award: R01GM118854

Burroughs Wellcome Fund, Award: Career Award at the Scientific Interface

Kinship Foundation, Award: Searle Scholarship

Pew Charitable Trusts, Award: Pew Scholarship

Alfred P. Sloan Foundation, Award: Sloan Fellowship

National Human Genome Research Institute, Award: T32HG00035

Howard Hughes Medical Institute, Award: Faculty Scholar Award