Genome evolution induced by chromatin structure and DNA methylation

自然选择和中性进化理论对于理解遗传变异和进化至关重要。在这项研究中，我们研究了染色质结构和DNA甲基化是否可能影响遗传变异和进化。事实上，我们发现了一个意想不到的基因组范围内的CpG甲基化状态的作用，作为一个主要的决定因素，近端的自然遗传变异。约18%的人类基因组位于CpG位点的10 bp范围内;在这些区域中，如果相邻CpG位点甲基化，单核苷酸多态性率显著增加约50%（P<E-566）。在两个青鳉近交系中，我们观察到一个独特的~200碱基对的周期性模式的遗传变异下游的转录起始位点及其与染色质结构的相关性。这些数据证实了遗传活性（转录）、DNA甲基化和染色质结构在进化时间尺度上对DNA序列的塑造做出贡献的潜力。

Natural selection and neutral theory of evolution have been crucial to understand genetic variation and evolution. In this study, we have examined whether chromatin structure and DNA methylation might affect genetic variation and evolution. Indeed, we identified an unexpected genome-wide role of the CpG methylation state as a major determinant of proximal natural genetic variation. ~18% of the human genome was within 10 bp of a CpG site; in these regions, the single nucleotide polymorphism rate significantly increased by ~50% (P<E-566) if the neighboring CpG sites are methylated. In two medaka inbred strains, we observed a distinctive ~200-base pair periodic pattern of genetic variation downstream of transcription start sites and its correlation with the chromatin structure. These data exemplify the potential for genetic activity (transcription), DNA methylation, and chromatin structure to contribute to molding the DNA sequence on an evolutionary time scale.