DNA methylation in the germline is among the most important factors influencing the evolution of mammalian genomes. Yet little is known about its evolutionary rate or the fraction of the methylome that has undergone change. We compared whole-genome, single-CpG DNA methylation profiles in sperm of seven species—human, chimpanzee, gorilla, rhesus macaque, mouse, rat, and dog—to investigate epigenomic evolution. We developed a phylo-epigenetic model for DNA methylation that accommodates the correlation of states at neighboring sites and allows for inference of ancestral states. Applying this model to the sperm methylomes, we uncovered an overall evolutionary expansion of the hypomethylated fraction of the genome, driven both by the birth of new hypomethylated regions and by extensive widening of hypomethylated intervals in ancestral species. This expansion shows strong lineage-specific aspects, most notably that hypomethylated intervals around transcription start sites have evolved to be considerably wider in primates and dog than in rodents, whereas rodents show evidence of a greater trend toward birth of new hypomethylated regions. Lineage-specific hypomethylated regions are enriched near sets of genes with common developmental functions and significant overlap across lineages. Rodent-specific and primate-specific hypomethylated regions are enriched for binding sites of similar transcription factors, suggesting that the plasticity accommodated by certain regulatory factors is conserved, despite substantial change in the specific sites of regulation. Overall our results reveal substantial global epigenomic change in mammalian sperm methylomes and point to a divergence in trans-epigenetic mechanisms that govern the organization of epigenetic states at gene promoters.

种系中的 DNA 甲基化是影响哺乳动物基因组进化的最重要因素之一。然而，人们对它的进化速度或发生变化的甲基化组的比例知之甚少。我们比较了人类、黑猩猩、大猩猩、恒河猴、小鼠、大鼠和狗这 7 个物种精子的全基因组、单 CpG DNA 甲基化谱，以研究表观基因组进化。我们开发了一种 DNA 甲基化的系统表观遗传模型，该模型适应邻近位点的状态相关性，并允许推断祖先状态。将该模型应用于精子甲基化组，我们发现了基因组低甲基化部分的整体进化扩展，这是由新的低甲基化区域的诞生和祖先物种中低甲基化区间的广泛扩大所驱动的。这种扩展显示出强烈的谱系特异性，最值得注意的是，灵长类动物和狗的转录起始位点周围的低甲基化间隔已经进化得比啮齿类动物宽得多，而啮齿类动物则显示出新的低甲基化区域诞生的更大趋势。谱系特异性低甲基化区域在具有共同发育功能且跨谱系显着重叠的基因组附近富集。啮齿类动物特异性和灵长类动物特异性低甲基化区域富含相似转录因子的结合位点，这表明尽管特定调节位点发生了实质性变化，但某些调节因子所适应的可塑性是保守的。 总的来说，我们的结果揭示了哺乳动物精子甲基化组中显着的全球表观基因组变化，并指出控制基因启动子表观遗传状态组织的反式表观遗传机制存在分歧。