Inferring DNA methylation in non-skeletal tissues of ancient specimens

Genome-wide premortem DNA methylation patterns can be computationally reconstructed from high-coverage DNA sequences of ancient samples. Because DNA methylation is more conserved across species than across tissues, and ancient DNA is typically extracted from bones and teeth, previous works utilizing...

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Autores: Mathov, Yoav, Nissim Rafinia, Malka, Leibson, Chen, Galun, Nir, Marquès i Bonet, Tomàs, 1975-, Kandel, Arye, Liebergal, Meir, Meshorer, Eran, Carmel, Liran
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/69133
Acesso em linha:http://hdl.handle.net/10230/69133
http://dx.doi.org/10.1038/s41559-024-02571-w
Access Level:acceso abierto
Palavra-chave:Epigenetics
Epigenomics
Evolutionary genetics
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dc.title.none.fl_str_mv Inferring DNA methylation in non-skeletal tissues of ancient specimens
title Inferring DNA methylation in non-skeletal tissues of ancient specimens
spellingShingle Inferring DNA methylation in non-skeletal tissues of ancient specimens
Mathov, Yoav
Epigenetics
Epigenomics
Evolutionary genetics
title_short Inferring DNA methylation in non-skeletal tissues of ancient specimens
title_full Inferring DNA methylation in non-skeletal tissues of ancient specimens
title_fullStr Inferring DNA methylation in non-skeletal tissues of ancient specimens
title_full_unstemmed Inferring DNA methylation in non-skeletal tissues of ancient specimens
title_sort Inferring DNA methylation in non-skeletal tissues of ancient specimens
dc.creator.none.fl_str_mv Mathov, Yoav
Nissim Rafinia, Malka
Leibson, Chen
Galun, Nir
Marquès i Bonet, Tomàs, 1975-
Kandel, Arye
Liebergal, Meir
Meshorer, Eran
Carmel, Liran
author Mathov, Yoav
author_facet Mathov, Yoav
Nissim Rafinia, Malka
Leibson, Chen
Galun, Nir
Marquès i Bonet, Tomàs, 1975-
Kandel, Arye
Liebergal, Meir
Meshorer, Eran
Carmel, Liran
author_role author
author2 Nissim Rafinia, Malka
Leibson, Chen
Galun, Nir
Marquès i Bonet, Tomàs, 1975-
Kandel, Arye
Liebergal, Meir
Meshorer, Eran
Carmel, Liran
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Epigenetics
Epigenomics
Evolutionary genetics
topic Epigenetics
Epigenomics
Evolutionary genetics
description Genome-wide premortem DNA methylation patterns can be computationally reconstructed from high-coverage DNA sequences of ancient samples. Because DNA methylation is more conserved across species than across tissues, and ancient DNA is typically extracted from bones and teeth, previous works utilizing ancient DNA methylation maps focused on studying evolutionary changes in the skeletal system. Here we suggest that DNA methylation patterns in one tissue may, under certain conditions, be informative on DNA methylation patterns in other tissues of the same individual. Using the fact that tissue-specific DNA methylation builds up during embryonic development, we identified the conditions that allow for such cross-tissue inference and devised an algorithm that carries it out. We trained the algorithm on methylation data from extant species and reached high precisions of up to 0.92 for validation datasets. We then used the algorithm on archaic humans, and identified more than 1,850 positions for which we were able to observe differential DNA methylation in prefrontal cortex neurons. These positions are linked to hundreds of genes, many of which are involved in neural functions such as structural and developmental processes. Six positions are located in the neuroblastoma breaking point family (NBPF) gene family, which probably played a role in human brain evolution. The algorithm we present here allows for the examination of epigenetic changes in tissues and cell types that are absent from the palaeontological record, and therefore provides new ways to study the evolutionary impacts of epigenetic changes.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/69133
http://dx.doi.org/10.1038/s41559-024-02571-w
url http://hdl.handle.net/10230/69133
http://dx.doi.org/10.1038/s41559-024-02571-w
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nat Ecol Evol. 2025 Jan;9(1):153-65
info:eu-repo/grantAgreement/EC/H2020/864203
info:eu-repo/grantAgreement/ES/3PE/PID2021-126004NB-100
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
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spelling Inferring DNA methylation in non-skeletal tissues of ancient specimensMathov, YoavNissim Rafinia, MalkaLeibson, ChenGalun, NirMarquès i Bonet, Tomàs, 1975-Kandel, AryeLiebergal, MeirMeshorer, EranCarmel, LiranEpigeneticsEpigenomicsEvolutionary geneticsGenome-wide premortem DNA methylation patterns can be computationally reconstructed from high-coverage DNA sequences of ancient samples. Because DNA methylation is more conserved across species than across tissues, and ancient DNA is typically extracted from bones and teeth, previous works utilizing ancient DNA methylation maps focused on studying evolutionary changes in the skeletal system. Here we suggest that DNA methylation patterns in one tissue may, under certain conditions, be informative on DNA methylation patterns in other tissues of the same individual. Using the fact that tissue-specific DNA methylation builds up during embryonic development, we identified the conditions that allow for such cross-tissue inference and devised an algorithm that carries it out. We trained the algorithm on methylation data from extant species and reached high precisions of up to 0.92 for validation datasets. We then used the algorithm on archaic humans, and identified more than 1,850 positions for which we were able to observe differential DNA methylation in prefrontal cortex neurons. These positions are linked to hundreds of genes, many of which are involved in neural functions such as structural and developmental processes. Six positions are located in the neuroblastoma breaking point family (NBPF) gene family, which probably played a role in human brain evolution. The algorithm we present here allows for the examination of epigenetic changes in tissues and cell types that are absent from the palaeontological record, and therefore provides new ways to study the evolutionary impacts of epigenetic changes.This publication was made possible through the support of a grant from the John Templeton Foundation (grant ID 61739 to L.C. and E.M.). The opinions expressed in this publication are those of the authors and do not necessarily reflect the views of the John Templeton Foundation. This study was also funded by the Israel Science Foundation (grant no. 2436/22 to L.C.) and by the Ministry of Innovation, Science & Technology (grant no. grant 1001584586 to L.C. and E.M.). T.M.-B. is supported by funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 864203), PID2021-126004NB-100 (MICIIN/FEDER, UE), ‘Unidad de Excelencia María de Maeztu’, funded by the AEI (CEX2018-000792-M), NIH 1R01HG010898-01A1 and Secretaria d’Universitats i Recerca and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2021 SGR 00177). L.C. is the Snyder Granadar chair in Genetics. E.M. is the Arthur Gutterman Family Chair for Stem Cell Research. We wish to thank Avigal Be’er for the design of Fig. 1.Nature Research202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/69133http://dx.doi.org/10.1038/s41559-024-02571-wreponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNat Ecol Evol. 2025 Jan;9(1):153-65info:eu-repo/grantAgreement/EC/H2020/864203info:eu-repo/grantAgreement/ES/3PE/PID2021-126004NB-100© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/691332026-06-12T07:21:37Z
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