A research group led by Specially Appointed Associate Professor Ken-Ichi T. Suzuki at the Emerging Model Organisms Facility, Trans-Scale Biology Center at the National Institute for Basic Biology (NIBB), and Toshinori Hayashi, Professor at the Hiroshima University Amphibian Research Center, announced on October 2 that they successfully decoded the genome sequence of an inbred strain of the Iberian ribbed newt, which at 20 billion bases is seven times larger than the human genome and had been difficult to decode due to its high repetitive sequence content. The research revealed characteristics of repetitive sequences involved in genome expansion, gene expression regulation in organ regeneration, and genes involved in amphibian evolution and newt-specific reproductive behavior. The findings are expected to provide clues to understanding the mysterious life phenomena that newts possess. The results were published in iScience on September 9.
Newts, which are tailed amphibians, possess remarkable organ regeneration capabilities that allow them to restore lost or damaged tissues and organs to their original state, and have long played an important role in research on development and regeneration.
The Iberian ribbed newt, which has gained attention as a model organism in recent years, has an inbred strain established and maintained in Japan that is essential for biological research. Determination of the inbred strain genome was considered necessary for advancing research using this newt. However, while chromosome-level genome sequencing of the wild type was reported in February of this year, the massive genome, rich in repetitive sequences, was considered technically challenging.
The Iberian ribbed newt (Pleurodeles waltl) is a species of newt native to the Iberian Peninsula. It is easy to breed, reaches sexual maturity within one year, and fertilized eggs can be obtained year-round. It is maintained and managed under the National BioResource Project at the Hiroshima University Amphibian Research Center.
In this study, a domestic group conducting research using the newt (the Iberian Ribbed Newt Research Consortium) took the lead in tackling genome sequencing. The work was made possible by overcoming technical challenges through advances in high-precision long-read sequencing technology. The researchers also compared and analyzed the genome sequence with those of other vertebrates, including the axolotl (Mexican salamander), another tailed amphibian.
The results revealed that approximately 70% of the genome consisted of repetitive sequences, most of which were "transposons," sequences that move around within the genome. The repetitive sequences were found to greatly increase the distances between gene exons, between genes, and between genes and genomic sequences that regulate gene transcription (enhancers).
The research also revealed that genes important for the formation of a wide range of animal tissues and organs, such as the brain, eyes, internal organs, teeth, and bones—including Bmp4 (bone morphogenetic protein 4) and the MyoD gene, which is important for muscle formation—are likely lost in tailed amphibians.
Furthermore, the transcriptional regulatory region (enhancer) of the Sonic Hedgehog gene (Shh), which is important for limb formation, functions normally despite being positioned very far away. When mutations were introduced through genome editing into one of the special sequences required to accurately activate gene expression over these ultra-long distances, limb development remained normal, but abnormalities appeared in limb regeneration.
In addition, the study suggested that sodefrin, a female-attracting pheromone, may function as a pheromone as-is without the precursor being cleaved in the Iberian ribbed newt.
Suzuki commented: "Decoding the massive genome of the inbred Iberian ribbed newt, spanning approximately 20 billion bases, was initially extremely difficult to achieve. However, through the latest technological innovations, we were able to overcome major technical and cost barriers. Above all, it was the close collaboration among domestic researchers that led to the many biological discoveries made in this study. Looking ahead, by achieving complete chromosome-level sequencing, we hope that biological research leveraging the advantages of inbred strains will spread worldwide."
Journal Information
Publication: iScience
Title: The inbred newt genome unveils molecular mechanisms of behavior, development, and regeneration in urodele amphibians
DOI: 10.1016/j.isci.2025.113535
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.