GC content elevates mutation and recombination rates in the yeast <i>Saccharomyces cerevisiae</i>

Abstract

The chromosomes of many eukaryotes have regions of high GC content interspersed with regions of low GC content. In the yeast <i>Saccharomyces cerevisiae</i>, high-GC regions are often associated with high levels of meiotic recombination. In this study, we constructed <i>URA3</i> genes that differ substantially in their base composition [<i>URA3-AT</i> (31% GC), <i>URA3-WT</i> (43% GC), and <i>URA3-GC</i> (63% GC)] but encode proteins with the same amino acid sequence. The strain with <i>URA3-GC</i> had an approximately sevenfold elevated rate of <i>ura3</i> mutations compared with the strains with <i>URA3-WT</i> or <i>URA3-AT</i> 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 <i>URA3-GC</i> gene also had elevated rates of meiotic and mitotic recombination relative to the <i>URA3-AT</i> or <i>URA3-WT</i> genes. Thus, base composition has a substantial effect on the basic parameters of genome stability and evolution.