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

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. ; We thank Beth Shapiro and Richard Green (protocol development advice); Richard Mitchell, Peter Hotez, Aliaksandr Astrowski, Aviva Aiden, Sirui Zhou, Susannah Selber-Hnatiw, Guy Rouleau, Emil Karpinski, George Church, Saul Godinez, Zane Colaric, Shaiza Pasha, Galina Aglyamova, Jefferson Sinson, Anat Vivante, Sergei Kliver, Dimoklis Gkountaroulis, Camilo Chacón-Duque, Douglass Turner, Joel Cracraft, and Paul Sweet (discussions); Adam Fotos and Scistories (figures); Mahdi Sadr (videography); the Houston Zoo veterinary team, Dan Fisher, Hojun Song, Brandon Lyons, Ray Riley, and the Rosenthal Meat Science and Technology Center team at Texas A&M, Mary Thompson, and Stephen O’Brien (samples); Judah Aiden and Thomas Griggs (experiment assistance); and Ron Mathis (baseball pitching). E.L.A. acknowledges the McNair Medical Institute, NIH ENCODE (UM1HG009375), US-Israel Binational Science Foundation (2019276), and NSF-DBI-2021795. Center ...