Fast, accurate and automatic ancient nucleosome and methylation maps with epiPALEOMIX

Publication: Research - peer-reviewJournal article

DOI

  • Kristian Hanghøj
    Kristian HanghøjCentre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, 1350K Copenhagen, Denmark. Université de Toulouse, University Paul Sabatier, Laboratoire d'Anthropobiologie Moléculaire et d'Imagerie de Synthèse, CNRS UMR 5288, 31000 Toulouse, France Lorlando@snm.ku.dk.
  • Andaine Seguin
    Andaine SeguinCentre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, 1350K Copenhagen, Denmark. Danish National High-Throughput DNA Sequencing Center, Natural History Museum of Denmark, University of Copenhagen, Øster Farimagsgade 2D, 1353K Copenhagen, Denmark.
  • Mikkel Schubert
    Mikkel SchubertCentre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, 1350K Copenhagen, Denmark.
  • Tobias Madsen
  • Jakob Skou Pedersen
  • Eske Willerslev
    Eske WillerslevCentre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, 1350K Copenhagen, Denmark. Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Ludovic Orlando
    Ludovic OrlandoCentre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, 1350K Copenhagen, Denmark. Université de Toulouse, University Paul Sabatier, Laboratoire d'Anthropobiologie Moléculaire et d'Imagerie de Synthèse, CNRS UMR 5288, 31000 Toulouse, France Lorlando@snm.ku.dk.

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.

Original languageEnglish
JournalMolecular Biology and Evolution
Volume33
Issue number12
Pages (from-to)3284-3298
ISSN0737-4038
DOIs
StatePublished - 13 Sep 2016

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