The giant axolotl genome uncovers the evolution, scaling, and transcriptional control of complex gene loci

Siegfried Schloissnig, Akane Kawaguchi, Sergej Nowoshilow, Francisco Falcon, Leo Otsuki, Pietro Tardivo, Nataliya Timoshevskaya, Melissa C. Keinath, Jeramiah James Smith, S. Randal Voss, Elly M. Tanaka

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Vertebrates harbor recognizably orthologous gene complements but vary 100-fold in genome size. How chromosomal organization scales with genome expansion is unclear, and how acute changes in gene regulation, as during axolotl limb regeneration, occur in the context of a vast genome has remained a riddle. Here, we describe the chromosome-scale assembly of the giant, 32 Gb axolotl genome. Hi-C contact data revealed the scaling properties of interphase and mitotic chromosome organization. Analysis of the assembly yielded understanding of the evolution of large, syntenic multigene clusters, including the Major Histocompatibility Complex (MHC) and the functional regulatory landscape of the Fibroblast Growth Factor 8 (Axfgf8) region. The axolotl serves as a primary model for studying successful regeneration.

Original languageEnglish
Article numbere2017176118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number15
DOIs
StatePublished - Apr 13 2021

Bibliographical note

Funding Information:
We thank the Institute of Molecular Pathology (IMP) axolotl caretakers for their dedicated work. We are grateful to Alex Schleiffer, Roman Stocsits, Oleg Simakov, Jim Kaufman, and Anton Goloborodko for sharing the data, help with the analyses and advice, and Gordana Wutz, Yuka Taniguchi-Sugiura, Alex Vogt, and the VBCF NGS as well as the IMP IT department for advice and assistance. We thank Meinrad Busslinger for reading part of the manuscript. E.M.T. was supported by core funding from the IMP and ERC AdG 742046, RegGeneMems. A.K. was supported by a JSPS Postdoctoral Fellowship for Overseas Researchers. L.O. was supported by a fellowship from the HFSP. N.T., M.C.K., J.J.S., and S.R.V. were supported by NIH R24OD010435 and P40OD019794, and ARO W911NF1810168.

Funding Information:
ACKNOWLEDGMENTS. We thank the Institute of Molecular Pathology (IMP) axolotl caretakers for their dedicated work. We are grateful to Alex Schleiffer, Roman Stocsits, Oleg Simakov, Jim Kaufman, and Anton Golobor-odko for sharing the data, help with the analyses and advice, and Gordana Wutz, Yuka Taniguchi-Sugiura, Alex Vogt, and the VBCF NGS as well as the IMP IT department for advice and assistance. We thank Meinrad Busslinger for reading part of the manuscript. E.M.T. was supported by core funding from the IMP and ERC AdG 742046, RegGeneMems. A.K. was supported by a JSPS Postdoctoral Fellowship for Overseas Researchers. L.O. was supported by a fellowship from the HFSP. N.T., M.C.K., J.J.S., and S.R.V. were supported by NIH R24OD010435 and P40OD019794, and ARO W911NF1810168.

Publisher Copyright:
© This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).

Keywords

  • Axolotl
  • Genome assembly
  • Regeneration
  • Topological associating domains

ASJC Scopus subject areas

  • General

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