A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae.
A modified fluctuation assay reveals a natural mutator phenotype that drives mutation spectrum variation within Saccharomyces cerevisiae.
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DOI：
10.7554/elife.68285
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发表时间：
2021-09-15
期刊：
影响因子：
7.7
通讯作者：
Harris K
中科院分区：
文献类型：
--
作者：
Jiang P;Ollodart AR;Sudhesh V;Herr AJ;Dunham MJ;Harris K
尽管对酿酒酵母的研究为诱变和DNA修复提供了许多见解，但大多数工作都集中在少数实验室菌株上。关于S.酿酒酵母的DNA修复途径。在这里，我们使用自然多态性检测几个野生和驯化S之间的历史突变谱差异。酿酒酵母菌株。为了确定这些差异是否可能是由遗传突变率修饰剂引起的，我们使用了一种带有CAN 1报告基因的改良波动试验来测量16种分析菌株的从头突变率和光谱。我们测量了10倍范围的突变率，并确定了两个菌株具有独特的突变谱。这些菌株被称为AEQ和AAR，来自该小组的“马赛克啤酒”进化枝，并共享C > A突变的富集，这也在几种马赛克啤酒和混合起源菌株的基因组中分离的罕见变异中观察到。AEQ和AAR都是二倍体天然分离物CBS 1782的单倍体衍生物，其罕见的多态性也富集C > A，表明潜在的增变等位基因可能在自然界中是活跃的。我们使用质粒互补测试来表明AAR和AEQ在DNA修复基因OGG 1中共享一个增变等位基因，该基因切除8-氧代鸟嘌呤损伤，如果不修复，该损伤可能导致C > A突变。
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.
影响因子：
3.3
作者：
Shockley AH;Doo DW;Rodriguez GP;Crouse GF
通讯作者：
Crouse GF