Although mutation rates have been extensively studied, variation in mutation rates throughout the genome is poorly understood. To understand patterns of genetic variation, it is important to understand how mutation rates vary. Chromatin modifications may be an important factor in determining variation in mutation rates in eukaryotic genomes. To study variation in mutation rates, we performed a mutation accumulation (MA) experiment in the filamentous fungus Neurospora crassa and sequenced the genomes of the 40 MA lines that had been propagated asexually for approximately 1015 mitoses. We detected 1322 mutations in total and observed that the mutation rate was higher in regions of low GC, in domains of H3K9 trimethylation, in centromeric regions, and in domains of H3K27 trimethylation. The rate of single-nucleotide mutations in euchromatin was . In contrast, the mutation rate in H3K9me3 domains was 10-fold higher: 2.43 . We also observed that the spectrum of single-nucleotide mutations was different between H3K9me3 and euchromatic domains. Our statistical model of mutation rate variation predicted a moderate amount of extant genetic variation, suggesting that the mutation rate is an important factor in determining levels of natural genetic variation. Furthermore, we characterized mutation rates of structural variants, complex mutations, and the effect of local sequence context on the mutation rate. Our study highlights that chromatin modifications are associated with mutation rates, and accurate evolutionary inferences should take variation in mutation rates across the genome into account.

中文翻译：

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染色质结构影响粗糙脉孢菌自发突变的速率和谱

尽管对突变率进行了广泛研究，但对整个基因组突变率的变化知之甚少。要了解遗传变异的模式，重要的是要了解突变率是如何变化的。染色质修饰可能是决定真核基因组突变率变化的重要因素。为了研究突变率的变化，我们在丝状真菌粗糙脉孢菌中进行了突变积累 (MA) 实验，并对已经无性繁殖了大约 1015 年的 40 个 MA 品系的基因组进行了测序有丝分裂。我们总共检测到 1322 个突变，观察到突变率在低 GC 区域、H3K9 三甲基化区域、着丝粒区域和 H3K27 三甲基化区域较高。常染色质中的单核苷酸突变率为. 相比之下，H3K9me3 域的突变率高 10 倍：2.43. 我们还观察到 H3K9me3 和常染色质结构域的单核苷酸突变谱不同。我们的突变率变异统计模型预测了适量的现存遗传变异，表明突变率是决定自然遗传变异水平的重要因素。此外，我们描述了结构变异的突变率、复杂突变以及局部序列上下文对突变率的影响。我们的研究强调染色质修饰与突变率相关，准确的进化推断应该考虑整个基因组突变率的变化。