The Mutational Profile of the Yeast Genome Is Shaped by Replication
The Mutational Profile of the Yeast Genome Is Shaped by Replication
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DOI：
10.1093/molbev/msr280
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发表时间：
2012-03-01
影响因子：
10.7
通讯作者：
Fischer, Gilles
中科院分区：
文献类型：
--
作者：
Agier, Nicolas;Fischer, Gilles
尽管多年来一直针对酵母基因组进行审查，但关于复制对酿酒酵母中取代动力学的影响知之甚少。在这里，我们表明，突变率增加与复制时间超过30%之间的最早和最新的复制区域。此外，我们发现了与复制极性相关的突变不对称性，导致前导链中C和A的取代率高于G和T（滞后链中G和T的取代率更高）。这种突变的不对称性在长期的进化过程中应该会在两条DNA链之间产生成分上的偏差。因此，我们表明，在S的基因组中，领先的复制链呈现出C超过G和A超过T的过量。酿酒酵母（在落后链中G + T超过C + A）。我们还表明，突变平衡时的核苷酸频率预测平衡时的组成偏斜非常接近于观察到的前导链和滞后链之间的偏斜，这表明在目前的S基因组中几乎已经达到了组成平衡。啤酒。令人惊讶的是，这种倾斜的方向与人类基因组中的方向相反。
Despite the scrutiny that has been directed for years at the yeast genome, relatively little is known about the impact of replication on the substitution dynamics in Saccharomyces cerevisiae. Here, we show that the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions. In addition, we found a mutational asymmetry associated with the polarity of replication resulting in higher rates of substitutions toward C and A than toward G and T in leading strands (reciprocally more substitutions toward G and T in lagging strands). Such mutational asymmetries applied over long evolutionary periods should generate compositional skews between the two DNA strands. Thus, we show that the leading replicating strands present an excess of C over G and of A over T in the genome of S. cerevisiae (reciprocally an excess of G + T over C + A in lagging strands). We also show that the nucleotide frequencies at mutational equilibrium predict a compositional skew at equilibrium very close to the observed skew between leading and lagging strands, suggesting that compositional equilibrium has been nearly attained in the present day genome of S. cerevisiae. Surprisingly, the direction of this skew is inverted compared with the one in the human genome.