Mapping of a gigantic salamander genome reveals secrets of regeneration
Researchers at Karolinska Institutet have mapped the genome of the Iberian ribbed newt and revealed how the composition and organization of the DNA are linked to its ability to regenerate entire body parts.
Salamanders are known for their unique ability to regenerate entire body parts and for their resistance to tumor development. The molecular mechanisms behind these traits have been difficult to study due to a lack of knowledge about the composition of their genome. Researchers at Karolinska Institutet have now succeeded in mapping the genome of the Iberian ribbed newt, providing new insights into these fascinating processes.
"We have mapped the genome of the Iberian ribbed newt, whose DNA amount is six times larger than that of humans and filled with short non-coding sequences, repeated throughout the genome. This has been a technical challenge, but we have succeeded with a detailed mapping which ismore comprehensive than in any other species with a similar genome size," says András Simon, professor at the Department of Cell and Molecular Biology.
By using advanced sequencing methods, the researchers have been able to determine the exact positions of both protein-coding and non-coding sequences on each chromosome. This has given them knowledge about how certain non-coding DNA sequences shape the genome’s composition and how these are regulated when an arm regrows.
"We have identified which protein-coding genes are missing in the salamander’s genome or have more copies than other species. The results are an important resource for researchers in several fields, such as genome evolution, regenerative and developmental biology, as well as cancer biology," explains Ketan Mishra, Ph.D. student in Simon lab at the same department.
The next step in the research is to focus on functional studies, where the researchers will manipulate molecular processes to determine how these affect the regenerative ability. They also plan to conduct comparative studies with other species to further understand these mechanisms.
The work was carried out in close collaboration with the Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany, and Lund University, Sweden
The study, published in the scientific journal Cell Genomics, and has been funded among other sources by grants from the European Research Council (ERC), Knut and Alice Wallenberg Foundation (KAW), Cancer Society, and Swedish Research Council to Andras Simon.
Publication
"Chromosome-scale genome assembly reveals how repeat elements shape non-coding RNA landscapes active during newt limb regeneration", Brown T, Mishra K, Elewa A, Iarovenko S, Subramanian E, Araus AJ, Petzold A, Fromm B, Friedländer MR, Rikk L, Suzuki M, Suzuki KT, Hayashi T, Toyoda A, Oliveira CR, Osipova E, Leigh ND, Yun MH, Simon A,
Cell Genom, online 27 January 2025, doi: 10.1016/j.xgen.2025.100761