Department of Molecular Medicine (MOMA), Aarhus University Hospital, Skejby, DK-8200 Aarhus N, Denmark;
Genome Res. 2014 Mar;24(3):454-66. doi: 10.1101/gr.163592.113. Epub 2013 Dec 3.
Epigenetic information is available from contemporary organisms, but is difficult to track back in evolutionary time. Here, we show that genome-wide epigenetic information can be gathered directly from next-generation sequence reads of DNA isolated from ancient remains. Using the genome sequence data generated from hair shafts of a 4000-yr-old Paleo-Eskimo belonging to the Saqqaq culture, we generate the first ancient nucleosome map coupled with a genome-wide survey of cytosine methylation levels. The validity of both nucleosome map and methylation levels were confirmed by the recovery of the expected signals at promoter regions, exon/intron boundaries, and CTCF sites. The top-scoring nucleosome calls revealed distinct DNA positioning biases, attesting to nucleotide-level accuracy. The ancient methylation levels exhibited high conservation over time, clustering closely with modern hair tissues. Using ancient methylation information, we estimated the age at death of the Saqqaq individual and illustrate how epigenetic information can be used to infer ancient gene expression. Similar epigenetic signatures were found in other fossil material, such as 110,000- to 130,000-yr-old bones, supporting the contention that ancient epigenomic information can be reconstructed from a deep past. Our findings lay the foundation for extracting epigenomic information from ancient samples, allowing shifts in epialleles to be tracked through evolutionary time, as well as providing an original window into modern epigenomics.
表观遗传信息可从现代生物中获取，但很难在进化时间上进行追溯。在这里，我们展示了可以从古代遗骸中提取的 DNA 的下一代测序读取中直接获取全基因组表观遗传信息。我们利用从属于 Saqqaq 文化的一位 4000 年前的古爱斯基摩人毛发轴生成的基因组序列数据，生成了第一个与全基因组胞嘧啶甲基化水平调查相结合的古代核小体图谱。通过在启动子区域、外显子/内含子边界和 CTCF 位点回收预期信号，验证了核小体图谱和甲基化水平的有效性。得分最高的核小体调用揭示了独特的 DNA 定位偏倚，证明了核苷酸水平的准确性。古老的甲基化水平随着时间的推移表现出高度的保守性，与现代毛发组织紧密聚类。利用古代甲基化信息，我们估计了 Saqqaq 个体的死亡年龄，并说明了如何利用表观遗传信息来推断古代基因表达。在其他化石材料中也发现了类似的表观遗传特征，例如 11 万至 13 万年前的骨骼，支持了从远古重建古代表观基因组信息的观点。我们的研究结果为从古代样本中提取表观基因组信息奠定了基础，允许通过进化时间追踪等位基因的变化，并为现代表观基因组学提供了一个原始窗口。
