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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2018-07, Vol.115 (30), p.E7109-E7118
• Main Authors: Kiktev, Denis A., Sheng, Ziwei, Lobachev, Kirill S., Petes, Thomas D.
• Format: Article
• Language: English
• Subjects: Amino acid sequence; Amino acids; Baking yeast; Base composition; Biological Sciences; Chromosomes; Composition effects; Deoxyribonucleic acid; DNA; DNA polymerase; DNA-directed DNA polymerase; Eukaryotes; Gc gene; Genes; Genomes; Meiosis; Mutation; PNAS Plus; Proteins; Recombination; Saccharomyces cerevisiae; Slippage; Yeast; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1807334115

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.