Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome

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Dokumenter

Jakob Skou Pedersen, Eivind Valen, Amhed Missael Vargas Velazquez, Brian John 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 Gustav Sandelin, M. Thomas P. Gilbert, Anders Krogh, Eske Willerslev & 1 andre Ludovic Antoine Alexandre Orlando

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.
OriginalsprogEngelsk
TidsskriftGenome Research
Vol/bind24
Udgave nummer3
Sider (fra-til)454-466
Antal sider13
ISSN1088-9051
DOI
StatusUdgivet - 2014

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