Towards ancient epigenomes - the first nucleosome and methylation map from an ancient human

In 2010, the DNA molecules preserved in a 4,000 year-old tuft of hair found in Greenland’s permafrost delivered the first ancient human genome ever characterized. Now, three years later we have developed a new computational method to reconstruct nucleosome and methylation maps from this ancient genome based purely on genomic sequencing information. These maps can reveal which genes were expressed in the ancient individual, opening up an exciting new field in the study of ancient samples.

HFSP Long-Term Fellow Eivind Valen and colleagues
authored on Tue, 14 January 2014

Three years ago, using the 4,000 year-old tuft of hair, DNA molecules were isolated, sequenced and assembled producing the first ancient human genome. Our study reanalyzed this data and produced the first ever ancient nucleosome and methylation map reconstructed from untreated DNA samples. Nucleosomes protect DNA from degradation and as a result, nucleosome-occupied regions are better preserved than nucleosome-free regions. This results in a higher frequency of sequence reads in occupied regions. Similarly, a certain type of DNA degradation will preclude sequencing unless the DNA base was originally methylated. Using a computational normalization method accounting for inherent sequencing biases we derived the nucleosome and methylation occupancy directly from the sequencing coverage across the ancient genome.

Figure: Spectrogram of the distribution of sequencing reads around the first exon of genes from the ancient individual reveal a strong periodicity of ~190bp downstream of the transcription start site. This periodicity is consistent with nucleosome phasing at active genes.

Since nucleosome positioning and DNA methylation marks participate in the regulation of gene expression, these maps were used to infer the expression levels in the hair tissue of the ancient human. This analysis confirmed the expression of a range of known hair-specific markers. The signatures of post-mortem DNA damage can therefore be used for quantifying gene expression levels in ancient individuals and provide functional information from ancient samples.

This study opens a new avenue in evolutionary biology as ancient DNA samples can now be used to reveal both genetic and epigenetic changes over evolutionary time and disentangle their respective role in the face of major historical environmental changes.


Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome. Jakob Skou Pedersen, Eivind Valen, Amhed M Vargas Velazquez, Brian J Parker, Morten Rasmussen, Stinus Lindgreen, Berit Lilje, Desmond J Tobin, Theresa K Kelly, Søren Vang, Robin Andersson, Peter A Jones, Cindi A Hoover Alexei Tikhonov, Egor Prokhortchouk, Edward M Rubin, Albin Sandelin, M. Thomas P Gilbert, Anders Krogh, Eske Willerslev and Ludovic Orlando. Genome Research. December 3, 2013, doi: 10.1101/gr.163592.

Link to abstract