title: Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome.
abstract: 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.
authors.affiliation: Department of Molecular Medicine (MOMA), Aarhus University Hospital, Skejby, DK-8200 Aarhus N, Denmark;
authors.forename: Jakob Skou
authors.initials: JS
authors.lastname: Pedersen
authors.forename: Eivind
authors.initials: E
authors.lastname: Valen
authors.forename: Amhed M Vargas
authors.initials: AM
authors.lastname: Velazquez
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Parker
authors.forename: Morten
authors.initials: M
authors.lastname: Rasmussen
authors.forename: Stinus
authors.initials: S
authors.lastname: Lindgreen
authors.forename: Berit
authors.initials: B
authors.lastname: Lilje
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Tobin
authors.forename: Theresa K
authors.initials: TK
authors.lastname: Kelly
authors.forename: Søren
authors.initials: S
authors.lastname: Vang
authors.forename: Robin
authors.initials: R
authors.lastname: Andersson
authors.forename: Peter A
authors.initials: PA
authors.lastname: Jones
authors.forename: Cindi A
authors.initials: CA
authors.lastname: Hoover
authors.forename: Alexei
authors.initials: A
authors.lastname: Tikhonov
authors.forename: Egor
authors.initials: E
authors.lastname: Prokhortchouk
authors.forename: Edward M
authors.initials: EM
authors.lastname: Rubin
authors.forename: Albin
authors.initials: A
authors.lastname: Sandelin
authors.forename: M Thomas P
authors.initials: MT
authors.lastname: Gilbert
authors.forename: Anders
authors.initials: A
authors.lastname: Krogh
authors.forename: Eske
authors.initials: E
authors.lastname: Willerslev
authors.forename: Ludovic
authors.initials: L
authors.lastname: Orlando
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D003596:Cytosine / Q000378:metabolism*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics; D019143:Evolution, Molecular; D015870:Gene Expression; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D004930:Inuit / Q000235:genetics*; D009707:Nucleosomes / Q000235:genetics*; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D009707:Nucleosomes; D003596:Cytosine