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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Cell |
| Vol/bind | 187 |
| Udgave nummer | 14 |
| Sider (fra-til) | 3541-3562.e51 |
| Antal sider | 74 |
| ISSN | 0092-8674 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information: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 Chac\u00F3n-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 for Theoretical Biological Physics is supported by NSF-PHY-2019745, PHY-2210291 (to J.N.O.) and hardware donated by AMD. The Welch Foundation supported E.L.A. (Q-1866), J.N.O. (C-1792), and A.B.O.J. E.L.A. and M.A.M.-R. acknowledge NHGRI-RM1HG011016. M.A.M.-R. acknowledges Spanish Ministerio de Ciencia e Innovaci\u00F3n (PID2020-115696RB-I00) and ERC-609989 under the 7th Framework Program FP7/2007-2013. M.T.P.G. and J.A.R. acknowledge ERC-681396, DNRF-143, and NNF-21OC0070726. M.J.R. acknowledges NIH-R35-GM147467. L.D. acknowledges Swedish Research Council (2017-04647 and 2021-00625) and ERC 101054984 PrimiGenomes. A.R.-H. acknowledges PID2020-112557GB-I00 and CGL2017-83802-P. M.D.P. and B.J.Z.H. acknowledge NIGMS/R35-GM146852. A.L.R. acknowledges USFWS-AFE2129-F22AP01215, UIUC College of ACES Seed Grant, and Fulbright Denmark. M.V.P. acknowledges NSF-DMS1763272, NIH-R01-AR079150, LEO Foundation (LF-AW-RAM-19-400008, LF-OC-20-000611), and Keck Foundation WMKF-5634988. Genome assembly was performed in association with the DNA Zoo Consortium (www.dnazoo.org), which acknowledges support from Illumina, IBM, and Pawsey Supercomputing Center. M.T.P.G. and E.L.A. conceived of the project. M.A.M.-R. M.T.P.G. and E.L.A. oversaw analysis. V.P. I.S.P. N.I.P. A.V.P. and L.D. provided mammoth samples. M.S.-V. C.P.E. and O.D. developed PaleoHi-C, with contributions from S.S.T.M. B.O. A.G. E.S.L. M.T.P.G. and E.L.A. M.S.-V. C.P.E. and M.A.K. performed PaleoHi-C, with assistance from S.S.T.M. S.A.M. and P.L.P. S.A.R. N.A.L. N.A.S. P.L.P. E.A.K. and S.I.B. performed imaging experiments with coordination by O.D. M.V.P. N.B.R. and A.S.G. I.G.-T. R.C. J.P.F. and K.P. provided elephant samples. O.D. R.K. J.J. R.P.R. and A.D.O. performed Hi-C on modern samples. O.D. led development of genome assembly algorithms and performed assembly with assistance from D.W. S.S.B. M.S.S. J.A.R. M.A.M.-R. N.C.D. P.K. and A.R.-H. O.D. J.A.R. M.D. and C.F. performed bioinformatics analyses with assistance from M.V.P. D.W. M.S.S. G.M. and K.R. A.K. and M.J.R. performed CRUSH. O.D. E.L.A. and P.G.W. developed the chromoglass model with contributions from J.N.O. M.D.P. V.G.C. A.B.O.J. I.C. B.J.Z.H. R.M. and M.A.M.-R. Simulations were performed by I.C. (simple diffusion), B.J.Z.H. (degradation), and V.G.C. and A.B.O.J. (structure inference) with supervision by O.D. and E.L.A. M.D.P. and J.N.O. respectively. O.D. J.A.R. M.S.-V. C.P.E. A.L.R. V.G.C. J.N.O. P.G.W. E.S.L. M.A.M.-R. M.T.P.G. and E.L.A. wrote the manuscript with input from all authors. E.L.A. M.T.P.G. and L.D. are on the scientific advisory board of Colossal Biosciences and hold stock options. From 2021 to 2023, M.A.M.-R. received consulting honoraria from Acuity Spatial Genomics. E.L.A. and O.D. are inventors on US provisional patent applications 16/308,386 (E.L.A. and O.D. filed 12/7/2018), 16/247,502 (E.L.A. and O.D. 1/14/2019), and PCT/US2020/064704 (E.L.A. 12/11/2020) by the Baylor College of Medicine and the Broad Institute, relating to the assembly methods in this manuscript. The authors used generative AI to help perform, check, and typeset supplemental calculations (ChatGPT) and to create a soundtrack for Video S1 (ChatGPT and Suno.com). Afterward, the authors reviewed and edited as needed, and they take full responsibility for the publication's contents.
Funding Information:
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, and Camilo Chac\u00F3n-Duque (discussions); Adam Fotos and Scistories (figures); Mahdi Sadr (videography); the Houston Zoo veterinary team, Dan Fisher, Hojun Song, Brandon Lyons, and Ray Riley and the Rosenthal Meat Science and Technology Center team at Texas A&M, Mary Thompson, and Stephen O\u2019Brien (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 . CTBP is supported by NSF - PHY-2019745 , PHY-2210291 (to J.N.O.) and hardware donated by AMD. The Welch Foundation supported E.L.A. ( Q-1866 ), J.N.O. ( C-1792 ), and A.B.O.J. E.L.A. and M.A.M.-R. acknowledge NHGRI - RM1HG011016 . M.A.M.-R. acknowledges Spanish Ministerio de Ciencia e Innovaci\u00F3n ( PID2020-115696RB-I00 ) and ERC - 609989 under the 7th Framework Program FP7/2007-2013 . M.T.P.G. and J.A.R. acknowledge ERC - 681396 , DNRF - 143 , and NNF - 21OC0070726 . M.J.R. acknowledges NIH - R35-GM147467 . L.D. acknowledges Swedish Research Council ( 2017-04647 and 2021-00625 ) and ERC 101054984 PrimiGenomes. A.R.-H. acknowledges PID2020-112557GB-I00 and CGL2017-83802-P. M.D.P. and B.J.Z.H. acknowledge NIGMS / R35-GM146852 . A.L.R. acknowledges USFWS - AFE2129-F22AP01215 , UIUC College of ACES Seed Grant, and Fulbright Denmark. M.V.P. acknowledges NSF - DMS1763272 , NIH - R01-AR079150 , LEO Foundation ( LF-AW-RAM-19-400008 , LF-OC-20-000611 ), and Keck Foundation WMKF-5634988 . Genome assembly was performed in association with the DNA Zoo Consortium ( www.dnazoo.org ), which acknowledges support from Illumina, IBM, and Pawsey Supercomputing Center.
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