The cross-species characterization of evolutionary changes in the functional genome can facilitate the translation of genetic findings across species and the interpretation of the evolutionary basis underlying complex phenotypes. Yet, this has not been fully explored between cattle, sheep, goats, and other mammals. Here, we systematically characterized the evolutionary dynamics of DNA methylation and gene expression in three somatic tissues (i.e., brain, liver, and skeletal muscle) and sperm across seven mammalian species, including three ruminant livestock species (cattle, sheep, and goats), humans, pigs, mice, and dogs, by generating and integrating 160 DNA methylation and transcriptomic datasets. We demonstrate dynamic changes of DNA hypomethylated regions (HypoMRs) and hypermethylated regions (HyperMRs) in tissue-type manner across cattle, sheep, and goats. Specifically, based on the phylo-epigenetic model of DNA methylome, we identified a total of 25,074 HypoMR extension events specific to cattle, which participated in rewiring tissue-specific regulatory network. Furthermore, by integrating genome-wide association studies (GWAS) of 50 cattle traits, we provided novel insights into the genetic and evolutionary basis of complex phenotypes in cattle. Overall, our study provides a valuable resource for exploring the evolutionary dynamics of the functional genome and highlights the importance of cross-species characterization of multi-omics datasets for the evolutionary interpretation of complex phenotypes in cattle livestock.

中文翻译：

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跨物种比较 DNA 甲基化揭示了对牛、绵羊和山羊复杂性状遗传学的新见解

功能基因组进化变化的跨物种表征可以促进跨物种遗传发现的转化以及复杂表型背后进化基础的解释。然而，这一点尚未在牛、绵羊、山羊和其他哺乳动物之间得到充分探索。在这里，我们系统地表征了七种哺乳动物物种的三种体细胞组织（即大脑、肝脏和骨骼肌）和精子中 DNA 甲基化和基因表达的进化动力学，其中包括三种反刍动物物种（牛、绵羊和山羊），通过生成和整合 160 个 DNA 甲基化和转录组数据集，对人类、猪、小鼠和狗进行了研究。我们以组织类型的方式展示了牛、绵羊和山羊 DNA 低甲基化区域 (HypoMRs) 和高甲基化区域 (HyperMRs) 的动态变化。具体来说，基于DNA甲基化组的系统表观遗传模型，我们总共鉴定了25,074个牛特有的HypoMR延伸事件，这些事件参与了组织特异性调控网络的重新连接。此外，通过整合 50 个牛性状的全基因组关联研究 (GWAS)，我们为牛复杂表型的遗传和进化基础提供了新的见解。总的来说，我们的研究为探索功能基因组的进化动力学提供了宝贵的资源，并强调了多组学数据集的跨物种表征对于牛牲畜复杂表型的进化解释的重要性。