Phyloepigenetic comparison of apes

We have determined methylation state differences in the epigenomes of neutrophils purified from human and chimpanzee. We used deep sequencing of ends generated by digestion with a methylation-sensitive restriction enzyme, followed by analysis with the MetMap computational pipeline to infer methylation states from the sequencing data. Using the orangutan as an outgroup, analysis of DNA sequence substitutions in CG-dense regions that are either methylated or unmethylated in all three species indicates that methylation states in the neutrophil reflect methylation states in the germline. Differences in methylation states were not correlated with differences in the local genomic sequences, indicating that they can be determined independently of local DNA sequence. Methylation differences were not distributed randomly among the individuals we analyzed, but recapitulated the known phylogenetic relationships of the three species in a pattern consistent with their stable inheritance. This data provide the first comprehensive dataset indicating that epigenetic states are maintained as independent characters that are predictably transmitted within species. Heritable epigenetic differences such as those we have identified could readily have functional and adaptive consequences, and contribute to the phenotypic divergence of human and chimpanzee. Comparison of methylation states in a single, uncultered cell type from human and chimpanzee