Improved detection of methylation in ancient DNA

Susanna Sawyer; Pere Gelabert; Benjamin Yakir; Alejandro Llanos-Lizcano; Alessandra Sperduti; Luca Bondioli; Olivia Cheronet; Christine Neugebauer-Maresch; Maria Teschler-Nicola; Mario Novak; Ildikó Pap; Ildikó Szikossy; Tamás Hajdu; Vyacheslav Moiseyev; Andrey Gromov; Gunita Zariņa; Eran Meshorer; Liran Carmel; Ron Pinhasi

doi:10.1186/s13059-024-03405-5

Improved detection of methylation in ancient DNA

Susanna Sawyer (Corresponding author)
, Pere Gelabert
, Benjamin Yakir
, Alejandro Llanos-Lizcano
, Alessandra Sperduti
, Luca Bondioli
, Olivia Cheronet
, Christine Neugebauer-Maresch
, Maria Teschler-Nicola
, Mario Novak
, Ildikó Pap
, Ildikó Szikossy
, Tamás Hajdu
, Vyacheslav Moiseyev
, Andrey Gromov
, Gunita Zariņa
, Eran Meshorer
, Liran Carmel
, Ron Pinhasi (Corresponding author)

Publications: Contribution to journal › Article › Peer Reviewed

Abstract

Reconstructing premortem DNA methylation levels in ancient DNA has led to breakthrough studies such as the prediction of anatomical features of the Denisovan. These studies rely on computationally inferring methylation levels from damage signals in naturally deaminated cytosines, which requires expensive high-coverage genomes. Here, we test two methods for direct methylation measurement developed for modern DNA based on either bisulfite or enzymatic methylation treatments. Bisulfite treatment shows the least reduction in DNA yields as well as the least biases during methylation conversion, demonstrating that this method can be successfully applied to ancient DNA.

Original language	English
Article number	261
Journal	Genome Biology
Volume	25
Issue number	1
DOIs	https://doi.org/10.1186/s13059-024-03405-5
Publication status	Published - Dec 2024

Funding

Open access funding provided by University of Vienna. S.Sa. was funded by the Austrian Science Fund (FWF) M3108-G. P.G. was funded by the Austrian Science Fund (FWF) P\u201336433. A.L.L was funded by Colfuturo (Fundaci\u00F3n para el futuro de Colombia) during his MSc. L.C. and B.Y. were funded by Israel Science Foundation (ISF grant 2436/22). L.C. and E.M. were funded by grant 1001584586 from the knowledge center for forensic DNA Israel by the Israel Ministry of Innovation, Science & Technology. L.C. is the Snyder Granadar chair in Genetics. The biological anthropological work on V\u00E1c individuals was supported by the grant of the Hungarian Research, Development and Innovation Office [project numbers: FK128013; TH and IP], by the Bolyai Scholarship of the Hungarian Academy of Sciences (TH), and by the \u00DANKP-23\u20135 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund (TH). We would like to thank Nadin Rohland for helpful feedback on the laboratory process and Spencer Sawyer for input on bioinformatics. Kevin Pang and Andrew Cosgrove were the primary editors of this article and managed its editorial process and peer review in collaboration with the rest of the editorial team. The review history is available as Additional file 2.

Austrian Fields of Science 2012

106018 Human biology

Keywords

Ancient DNA
Bisulfite treatment
Enzymatic methylation treatment
Methylation
Paleogenomics

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10.1186/s13059-024-03405-5Licence: CC BY 4.0

https://phaidra.univie.ac.at/o:2120021Licence: CC BY 4.0

Cite this

Sawyer, S., Gelabert, P., Yakir, B., Llanos-Lizcano, A., Sperduti, A., Bondioli, L., Cheronet, O., Neugebauer-Maresch, C., Teschler-Nicola, M., Novak, M., Pap, I., Szikossy, I., Hajdu, T., Moiseyev, V., Gromov, A., Zariņa, G., Meshorer, E., Carmel, L., & Pinhasi, R. (2024). Improved detection of methylation in ancient DNA. Genome Biology, 25(1), Article 261. https://doi.org/10.1186/s13059-024-03405-5

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abstract = "Reconstructing premortem DNA methylation levels in ancient DNA has led to breakthrough studies such as the prediction of anatomical features of the Denisovan. These studies rely on computationally inferring methylation levels from damage signals in naturally deaminated cytosines, which requires expensive high-coverage genomes. Here, we test two methods for direct methylation measurement developed for modern DNA based on either bisulfite or enzymatic methylation treatments. Bisulfite treatment shows the least reduction in DNA yields as well as the least biases during methylation conversion, demonstrating that this method can be successfully applied to ancient DNA.",

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Sawyer, S , Gelabert, P, Yakir, B, Llanos-Lizcano, A, Sperduti, A, Bondioli, L, Cheronet, O , Neugebauer-Maresch, C, Teschler-Nicola, M, Novak, M, Pap, I, Szikossy, I, Hajdu, T, Moiseyev, V, Gromov, A, Zariņa, G, Meshorer, E, Carmel, L & Pinhasi, R 2024, 'Improved detection of methylation in ancient DNA', Genome Biology, vol. 25, no. 1, 261. https://doi.org/10.1186/s13059-024-03405-5

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AU - Bondioli, Luca

AU - Cheronet, Olivia

AU - Neugebauer-Maresch, Christine

AU - Teschler-Nicola, Maria

AU - Novak, Mario

AU - Pap, Ildikó

AU - Szikossy, Ildikó

AU - Hajdu, Tamás

AU - Moiseyev, Vyacheslav

AU - Gromov, Andrey

AU - Zariņa, Gunita

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Improved detection of methylation in ancient DNA

Abstract

Funding

Austrian Fields of Science 2012

Keywords

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