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DNA methylation in sperm is among the most important factors shaping evolution of the mammalian genome. By directly altering germline mutation rates, the DNA methylation system has shaped the CpG landscape of mammalian genomes, resulting in the CpG island phenomenon. Yet little is known about how this system itself has co-evolved with its substrate during mammalian evolution. We analyzed full-genome single-CpG DNA methylation profiles in sperm from human, chimp, gorilla, rhesus, mouse, rat and dog. Our results point to an evolutionary expansion of the unmethylated portion of mammalian genomes. Within the mutually orthologous genome this trend is driven both by the birth of unmethylated regions and by widening of intervals that are unmethylated in ancestors. We find strikingly divergent global features in rodents. At the same time, we observe the evolutionary emergence of methylome features in mouse sperm bears association with similar pathways to those found in human. Together,these results revealed general principles in mammalian epigenome evolution.Overall design: Genomic DNA form gorilla, rat and dog (1 gorilla individual; 2 rat individuals; 4 dog individuals; individuals sequenced separately) mature sperm was isolated, bisulfite converted and sequenced |