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Proc Natl Acad Sci U S A. 2018 Jul 24;115(30):E7109-E7118. doi: 10.1073/pnas.1807334115. Epub 2018 Jul 9.

GC content elevates mutation and recombination rates in the yeast Saccharomyces cerevisiae.

Author information

1
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710.
2
School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332.
3
Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332.
4
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710; tom.petes@duke.edu.

Abstract

The chromosomes of many eukaryotes have regions of high GC content interspersed with regions of low GC content. In the yeast Saccharomyces cerevisiae, high-GC regions are often associated with high levels of meiotic recombination. In this study, we constructed URA3 genes that differ substantially in their base composition [URA3-AT (31% GC), URA3-WT (43% GC), and URA3-GC (63% GC)] but encode proteins with the same amino acid sequence. The strain with URA3-GC had an approximately sevenfold elevated rate of ura3 mutations compared with the strains with URA3-WT or URA3-AT About half of these mutations were single-base substitutions and were dependent on the error-prone DNA polymerase ζ. About 30% were deletions or duplications between short (5-10 base) direct repeats resulting from DNA polymerase slippage. The URA3-GC gene also had elevated rates of meiotic and mitotic recombination relative to the URA3-AT or URA3-WT genes. Thus, base composition has a substantial effect on the basic parameters of genome stability and evolution.

KEYWORDS:

error-prone DNA polymerase; high GC content; meiotic recombination; mitotic recombination; mutations

PMID:
29987035
PMCID:
PMC6064992
DOI:
10.1073/pnas.1807334115
[Indexed for MEDLINE]
Free PMC Article

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