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

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; Ludovic Antoine Alexandre Orlando

doi:10.1101/gr.163592.113

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

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 WillerslevLudovic Antoine Alexandre Orlando

Computational and RNA Biology

90 Citations (Scopus)

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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.

Original language	English
Journal	Genome Research
Volume	24
Issue number	3
Pages (from-to)	454-466
Number of pages	13
ISSN	1088-9051
DOIs	https://doi.org/10.1101/gr.163592.113
Publication status	Published - Mar 2014

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Pedersen_2014_Genome-wide_nucleosomeFinal published version, 4.16 MBLicence: CC BY-NC

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Pedersen, J. S., Valen, E., Velazquez, A. M. V., Parker, B. J., Rasmussen, M., Lindgreen, S., Lilje, B., Tobin, D. J., Kelly, T. K., Vang, S., Andersson, R., Jones, P. A., Hoover, C. A., Tikhonov, A., Prokhortchouk, E., Rubin, E. M., Sandelin, A. G., Gilbert, M. T. P., Krogh, A., ... Orlando, L. A. A. (2014). Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome. Genome Research, 24(3), 454-466. https://doi.org/10.1101/gr.163592.113

Pedersen, JS, Valen, E, Velazquez, AMV, Parker, BJ, Rasmussen, M, Lindgreen, S, Lilje, B, Tobin, DJ, Kelly, TK, Vang, S, Andersson, R, Jones, PA, Hoover, CA, Tikhonov, A, Prokhortchouk, E, Rubin, EM, Sandelin, AG , Gilbert, MTP , Krogh, A , Willerslev, E & Orlando, LAA 2014, 'Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome', Genome Research, vol. 24, no. 3, pp. 454-466. https://doi.org/10.1101/gr.163592.113

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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.",

author = "Pedersen, {Jakob Skou} and Eivind Valen and Velazquez, {Amhed Missael Vargas} and Parker, {Brian John} and Morten Rasmussen and Stinus Lindgreen and Berit Lilje and Tobin, {Desmond J.} and Kelly, {Theresa K.} and S{\o}ren Vang and Robin Andersson and Jones, {Peter A.} and Hoover, {Cindi A.} and Alexei Tikhonov and Egor Prokhortchouk and Rubin, {Edward M.} and Sandelin, {Albin Gustav} and Gilbert, {M. Thomas P.} and Anders Krogh and Eske Willerslev and Orlando, {Ludovic Antoine Alexandre}",

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AU - Pedersen, Jakob Skou

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AU - Parker, Brian John

AU - Rasmussen, Morten

AU - Lindgreen, Stinus

AU - Lilje, Berit

AU - Tobin, Desmond J.

AU - Kelly, Theresa K.

AU - Vang, Søren

AU - Andersson, Robin

AU - Jones, Peter A.

AU - Hoover, Cindi A.

AU - Tikhonov, Alexei

AU - Prokhortchouk, Egor

AU - Rubin, Edward M.

AU - Sandelin, Albin Gustav

AU - Gilbert, M. Thomas P.

AU - Krogh, Anders

AU - Willerslev, Eske

AU - Orlando, Ludovic Antoine Alexandre

PY - 2014/3

Y1 - 2014/3

N2 - 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.

AB - 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.

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DO - 10.1101/gr.163592.113

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VL - 24

SP - 454

EP - 466

JO - Genome Research

JF - Genome Research

IS - 3

ER -

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

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