Domestication is one of the strongest examples of artificial selection and has produced some of the most extreme within-species phenotypic variation known. In the case of the chicken, it has been hypothesized that DNA methylation may play a mechanistic role in the domestication response. By inter-crossing wild-derived red junglefowl with domestic chickens, we mapped quantitative trait loci for hypothalamic methylation (methQTL), gene expression (eQTL) and behaviour. We find large, stable methylation differences, with 6,179 cis and 2,973 trans methQTL identified. Over 46% of the trans effects were genotypically controlled by five loci, mainly associated with increased methylation in the junglefowl genotype. In a third of eQTL, we find that there is a correlation between gene expression and methylation, while statistical causality analysis reveals multiple instances where methylation is driving gene expression, as well as the reverse. We also show that methylation is correlated with some aspects of behavioural variation in the inter-cross. In conclusion, our data suggest a role for methylation in the regulation of gene expression underlying the domesticated phenotype of the chicken.

驯化是人工选择最有力的例子之一，并产生了一些已知的最极端的种内表型变异。就鸡而言，假设 DNA 甲基化可能在驯化反应中发挥机制作用。通过将野生红原鸡与家鸡杂交，我们绘制了下丘脑甲基化 (methQTL)、基因表达 (eQTL) 和行为的数量性状位点。我们发现了大的、稳定的甲基化差异，确定了 6,179 个顺式和 2,973个反式甲基化QTL。超过 46% 的反式影响由五个位点进行基因型控制，主要与原鸡基因型中甲基化的增加有关。在三分之一的 eQTL 中，我们发现基因表达和甲基化之间存在相关性，而统计因果关系分析揭示了甲基化驱动基因表达的多个实例，反之亦然。我们还表明甲基化与杂交中行为变异的某些方面相关。总之，我们的数据表明甲基化在调节鸡驯化表型的基因表达中的作用。