Rate, spectrum, and evolutionary dynamics of spontaneous epimutations

Stochastic changes in cytosine methylation are a source of heritable epigenetic and phenotypic diversity in plants. Using the model plant Arabidopsis thaliana, we derive robust estimates of the rate at which methylation is spontaneously gained (forward epimutation) or lost (backward epimutation) at individual cytosines and construct a comprehensive picture of the epimutation landscape in this species. We demonstrate that the dynamic interplay between forward and backward epimutations is modulated by genomic context and show that subtle contextual differences have profoundly shaped patterns of methylation diversity in A. thaliana natural populations over evolutionary timescales. Theoretical arguments indicate that the epimutation rates reported here are high enough to rapidly uncouple genetic from epigenetic variation, but low enough for new epialleles to sustain long-term selection responses. Our results provide new insights into methylome evolution and its population-level consequences. Overall design: MethylC-seq of Arabidopsis thaliana

胞嘧啶甲基化的随机变化是植物可遗传表观遗传与表型多样性的来源之一。本研究以模式植物拟南芥（Arabidopsis thaliana）为实验材料，对单个胞嘧啶位点上甲基化自发获得的正向表观突变(epimutation)或丢失的反向表观突变(epimutation)速率进行了稳健估算，并构建了该物种表观突变景观的全面图谱。本研究证实，正向与反向表观突变间的动态互作受基因组背景调控，同时发现细微的基因组背景差异已在进化尺度上深刻塑造了拟南芥自然种群中的甲基化多样性模式。理论分析表明，本研究报道的表观突变速率足够高，可快速实现遗传变异与表观遗传变异的解耦，但又足够低，使得新表观等位基因(epialleles)能够维持长期选择响应。本研究结果为甲基化组(methylome)进化及其种群层面的效应提供了全新的见解。实验设计：拟南芥的甲基化测序(MethylC-seq)