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.

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Published in PNAS, v. 118, no. 15, e2017176118.

Copyright © 2021 the Author(s)

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

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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.

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