Data from: The concerted impact of domestication and transposon insertions on methylation patterns between dogs and gray wolves

The process of domestication can exert intense trait-targeted selection on genes and regulatory regions. Specifically, rapid shifts in the structure and sequence of genomic regulatory elements could provide an explanation for the extensive, and sometimes extreme, variation in phenotypic traits observed in domesticated species. Here, we explored methylation differences from >24,000 cytosines distributed across the genomes of the domesticated dog (Canis familiaris) and the gray wolf (C. lupus). PCA and model-based cluster analyses identified two primary groups, domestic versus wild canids. A scan for significantly differentially methylated sites (DMSs) revealed species-specific patterns at 68 sites after correcting for cell heterogeneity, with weak yet significant hyper-methylation typical of purebred dogs when compared to wolves (59% and 58%, p<0.05, respectively). Additionally, methylation patterns at eight genes significantly deviated from neutrality, with similar trends of hyper-methylation in purebred dogs. The majority (>66%) of differentially methylated regions contained or were associated with repetitive elements, indicative of a genotype-mediated trend. However, DMSs were also often linked to functionally relevant genes (e.g. neurotransmitters). Finally, we utilized known genealogical relationships among Yellowstone wolves to survey transmission stability of methylation marks, from which we found a substantial fraction that demonstrated high heritability (both H2 and h2>0.99). These analyses provide a unique epigenetic insight into the molecular consequences of recent selection and radiation of our most ancient domesticated companion, the dog. These findings suggest selection has acted on methylation patterns, providing a new genomic perspective on phenotypic diversification in domesticated species.

驯化过程可对基因及调控区域施加强烈的性状靶向选择压力。具体而言，基因组调控元件的结构与序列快速变化，或可解释驯化物种中广泛存在、有时甚至极端的表型性状变异。本研究针对驯化家犬（Canis familiaris）与灰狼（Canis lupus，C. lupus）基因组中分布的逾24000个胞嘧啶（cytosine）位点，探究其甲基化（methylation）差异。主成分分析（Principal Component Analysis, PCA）与基于模型的聚类分析成功区分出两大演化类群：驯化犬科动物与野生犬科动物。在校正细胞异质性（cell heterogeneity）后，对显著差异甲基化位点（significantly differentially methylated sites, DMSs）的扫描结果显示，68个位点呈现物种特异性模式；与灰狼相比，纯种犬呈现出微弱但显著的高甲基化（hyper-methylation）特征（分别为59%与58%，p<0.05）。此外，8个基因的甲基化模式显著偏离中性进化（neutrality）趋势，纯种犬同样呈现高甲基化的相似趋势。逾66%的差异甲基化区域（differentially methylated regions）包含或与重复序列元件（repetitive elements）相关，这一结果暗示了基因型介导的演化趋势。但显著差异甲基化位点同样常与功能相关基因（如神经递质（neurotransmitters）编码基因）关联。最后，本研究借助黄石公园灰狼已知的谱系关系，探究甲基化标记的传递稳定性，结果发现大量位点表现出极高的遗传力（heritability）：广义遗传力（H2）与狭义遗传力（h2）均大于0.99。本研究为解析人类最古老的驯化伴侣——家犬，在近期选择与辐射演化过程中的分子效应提供了独特的表观遗传学（epigenetic）视角。本研究结果表明，选择作用于甲基化模式，为驯化物种的表型多样化提供了全新的基因组学研究视角。