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本研究明确了从人类与黑猩猩体内纯化得到的中性粒细胞（neutrophil）表观基因组（epigenome）中的甲基化状态差异。我们采用甲基化敏感限制性内切酶（methylation-sensitive restriction enzyme）酶切产生的末端进行深度测序，随后通过MetMap计算流程分析测序数据，以从中推断甲基化状态。以红毛猩猩作为外类群，对三个物种中均呈甲基化或非甲基化状态的CG富集区域内的DNA序列替换进行分析后发现，中性粒细胞的甲基化状态能够反映生殖系（germline）的甲基化状态。甲基化状态差异与局部基因组序列差异无显著关联，表明甲基化状态可独立于局部DNA序列确立。在所分析的个体中，甲基化差异并非随机分布，而是重现了已知的三个物种的系统发育关系，其模式与稳定遗传的特征相符。本数据集为首份综合性数据集，证实表观基因组状态可作为独立性状得以维持，并能在物种内以可预测的方式传递。本研究发现的这类可遗传表观遗传差异，可轻易产生功能性与适应性后果，推动人类与黑猩猩的表型分化。对人类与黑猩猩单一未培养细胞类型的甲基化状态进行比较