Abstract
Salamanders exhibit an extraordinary ability among vertebrates to regenerate complex body parts. However, scarce genomic resources have limited our understanding of regeneration in adult salamanders. Here, we present the ~20 Gb genome and transcriptome of the Iberian ribbed newt Pleurodeles waltl, a tractable species suitable for laboratory research. We find that embryonic stem cell-specific miRNAs mir-93b and mir-427/430/302, as well as Harbinger DNA transposons carrying the Myb-like proto-oncogene have expanded dramatically in the Pleurodeleswaltl genome and are co-expressed during limb regeneration. Moreover, we find that a family of salamander methyltransferases is expressed specifically in adult appendages. Using CRISPR/Cas9 technology to perturb transcription factors, we demonstrate that, unlike the axolotl, Pax3 is present and necessary for development and that contrary to mammals, muscle regeneration is normal without functional Pax7 gene. Our data provide a foundation for comparative genomic studies that generate models for the uneven distribution of regenerative capacities among vertebrates.
Highlights
Salamanders exhibit an extraordinary ability among vertebrates to regenerate complex body parts
We describe the genome and transcriptome of P. waltl (Methods; Supplementary Methods, Supplementary Fig. 1b, and Supplementary Tables 1–5) as a resource to explore regeneration relevant novelties, and adapt CRISPR/Cas[9] technology to perturb key transcription factors involved in regeneration
The P. waltl haplotype genome size is ~20 Gb (Supplementary Table 1), making this one of the largest vertebrate genomes sequenced to date
Summary
Salamanders exhibit an extraordinary ability among vertebrates to regenerate complex body parts. The random manifestation of extensive regeneration capacities in the animal kingdom implies a phylogenetically widespread regeneration potential, which is masked in most species[1,2,3,4,5] Among tetrapods, salamanders, such as newts and axolotls, display the largest regenerative repertoire. In contrast to the paedomorphic axolotl, newts undergo metamorphosis, have a broader regeneration spectrum and mobilize additional cell sources for regeneration of the same body part[7]. Such interspecies differences among closely related species offer opportunities to reveal valuable information about the evolution of processes that allow or counteract regeneration. We describe the genome and transcriptome of P. waltl (Methods; Supplementary Methods, Supplementary Fig. 1b, and Supplementary Tables 1–5) as a resource to explore regeneration relevant novelties, and adapt CRISPR/Cas[9] technology to perturb key transcription factors involved in regeneration
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