Nucleosome organization has been suggested to affect local mutation rates in the genome. However, the lack of de novo mutation and high-resolution nucleosome data has limited the investigation of this hypothesis. Additionally, analyses using indirect mutation rate measurements have yielded contradictory and potentially confounding results. Here, we combine data on >300,000 human de novo mutations with high-resolution nucleosome maps and find substantially elevated mutation rates around translationally stable (‘strong’) nucleosomes. We show that the mutational mechanisms affected by strong nucleosomes are low-fidelity replication, insufficient mismatch repair and increased double-strand breaks. Strong nucleosomes preferentially locate within young SINE/LINE transposons, suggesting that when subject to increased mutation rates, transposons are then more rapidly inactivated. Depletion of strong nucleosomes in older transposons suggests frequent positioning changes during evolution. The findings have important implications for human genetics and genome evolution.

已经建议核小体组织影响基因组中的局部突变率。然而，缺乏从头突变和高分辨率核小体数据限制了这一假设的研究。此外，使用间接突变率测量的分析得出了矛盾的结果，并可能产生混淆。在这里，我们将有关> 300,000人类从头突变的数据与高分辨率核小体图相结合，并发现翻译稳定（“强”）核小体周围的突变率大大提高。我们表明受强核小体影响的突变机制是低保真复制，错配修复不足和增加的双链断裂。强核小体优先位于年轻的SINE / LINE转座子中，这表明当突变率增加时，然后转座子被更快地灭活。较老的转座子中强核小体的耗尽表明进化过程中频繁的定位变化。这些发现对人类遗传学和基因组进化具有重要意义。