Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample

Affiliations
  • 1Center for Evolutionary Hologenomics, University of Copenhagen, DK-1353 Copenhagen, Denmark.
  • 2The Center for Genome Architecture and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, USA. Electronic address: olga.dudchenko@bcm.edu.
  • 3Center for Evolutionary Hologenomics, University of Copenhagen, DK-1353 Copenhagen, Denmark; Centre Nacional d’Anàlisi Genòmica, CNAG, 08028 Barcelona, Spain.
  • 4Centre for Palaeogenetics, SE-106 91 Stockholm, Sweden; Department of Bioinformatics and Genetics, Swedish Museum of Natural History, 10405 Stockholm, Sweden; Department of Zoology, Stockholm University, SE-106 91 Stockholm, Sweden.
  • 5The Center for Genome Architecture and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • 6Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, USA.
  • 7Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • 8Department of Physics, Northeastern University, Boston, MA 02115, USA; Center for Theoretical Biological Physics, Northeastern University, Boston, MA 02215, USA.
  • 9The Center for Genome Architecture and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • 10Department of Animal Sciences and Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
  • 11Department of Developmental and Cell Biology, University of California-Irvine, Irvine, CA, 92697, USA.
  • 12Institute of Molecular and Cellular Biology SB RAS, Novosibirsk 630090, Russia.
  • 13Institute of Cytology and Genetics SB RAS, Novosibirsk 630090, Russia.
  • 14UWA School of Agriculture and Environment, University of Western Australia, Perth, WA 6009, Australia.
  • 15Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • 16San Antonio Zoo, San Antonio, TX 78212, USA.
  • 17Houston Zoo, Houston, TX 77030, USA.
  • 18Departament de Biologia Cel·lular, Fisiologia i Immunologia and Genome Integrity and Instability Group, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain.
  • 19Academy of Sciences of Sakha Republic, Yakutsk 677000, Russia.
  • 20Institute of Biological Problems of Cryolitezone SB RAS, Yakutsk 677000, Russia.
  • 21Academy of Sciences of Sakha Republic, Yakutsk 677000, Russia; North-Eastern Federal University, Yakutsk 677027, Russia.
  • 22Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 23Centre Nacional d’Anàlisi Genòmica, CNAG, 08028 Barcelona, Spain; Centre for Genomic Regulation, The Barcelona Institute for Science and Technology, 08003 Barcelona, Spain; ICREA, 08010 Barcelona, Spain; Universitat Pompeu Fabra, 08002 Barcelona, Spain. Electronic address: martirenom@cnag.eu.
  • 24Center for Evolutionary Hologenomics, University of Copenhagen, DK-1353 Copenhagen, Denmark; University Museum NTNU, 7012 Trondheim, Norway. Electronic address: tgilbert@sund.ku.dk.

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Abstract

Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth’s death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale.

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