Fast, Accurate and Automatic Ancient Nucleosome and Methylation Maps with epiPALEOMIX.
The first epigenomes from archaic hominins (AH) and ancient anatomically modern humans (AMH) have recently been characterized, based, however, on a limited number of samples. The extent to which ancient genome-wide epigenetic landscapes can be reconstructed thus remains contentious. Here, we present epiPALEOMIX, an open-source and user-friendly pipeline that exploits post-mortem DNA degradation patterns to reconstruct ancient methylomes and nucleosome maps from shotgun and/or capture-enrichment data. Applying epiPALEOMIX to the sequence data underlying 35 ancient genomes including AMH, AH, equids and aurochs, we investigate the temporal, geographical and preservation range of ancient epigenetic signatures. We first assess the quality of inferred ancient epigenetic signatures within well-characterized genomic regions. We find that tissue-specific methylation signatures can be obtained across a wider range of DNA preparation types than previously thought, including when no particular experimental procedures have been used to remove deaminated cytosines prior to sequencing. We identify a large subset of samples for which DNA associated with nucleosomes is protected from post-mortem degradation, and nucleosome positioning patterns can be reconstructed. Finally, we describe parameters and conditions such as DNA damage levels and sequencing depth that limit the preservation of epigenetic signatures in ancient samples. When such conditions are met, we propose that epigenetic profiles of CTCF binding regions can be used to help data authentication. Our work, including epiPALEOMIX, opens for further investigations of ancient epigenomes through time especially aimed at tracking possible epigenetic changes during major evolutionary, environmental, socioeconomic, and cultural shifts.
Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.|Laboratoire d'Anthropobiologie Moléculaire et d'Imagerie de Synthèse, Université de Toulouse, University Paul Sabatier, Toulouse, France.
Kristian
K
Hanghøj
Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.|Danish National High-Throughput DNA Sequencing Center, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.
Andaine
A
Seguin-Orlando
Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.
Mikkel
M
Schubert
Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.|Bioinformatics Research Centre (BiRC), Aarhus University, Aarhus, Denmark.
Tobias
T
Madsen
Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.|Bioinformatics Research Centre (BiRC), Aarhus University, Aarhus, Denmark.
Jakob Skou
JS
Pedersen
Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.|Department of Zoology, University of Cambridge, Cambridge, United Kingdom.|Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom.
Eske
E
Willerslev
Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark lorlando@snm.ku.dk.|Laboratoire d'Anthropobiologie Moléculaire et d'Imagerie de Synthèse, Université de Toulouse, University Paul Sabatier, Toulouse, France.
Ludovic
L
Orlando
D042002:Chromatin Assembly and Disassembly; D003198:Computer Simulation; D003596:Cytosine / Q000378:metabolism; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D000072441:DNA, Ancient / Q000032:analysis*; D044127:Epigenesis, Genetic; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D009707:Nucleosomes / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software
D000072441:DNA, Ancient; D009707:Nucleosomes; D003596:Cytosine; D004247:DNA
DNA methylation; ancient DNA; epigenome; nucleosome.