The Secret of Longevity in the DNA of the Shark That Lives Up to 400 Years

The Greenland shark (Somniosus microcephalus) is the vertebrate with the highest life expectancy: 400 years, making it the longest-lived in the world. But what is the secret of these “Methuselahs” of the oceans? An international …

The Secret of Longevity in the DNA of the Shark That Lives Up to 400 Years

The Greenland shark (Somniosus microcephalus) is the vertebrate with the highest life expectancy: 400 years, making it the longest-lived in the world. But what is the secret of these “Methuselahs” of the oceans? An international team of scientists from institutes such as the Fritz Lipmann Institute on Aging in Jena, Germany, and the Scuola Normale Superiore in Pisa has mapped the genome of the animal, which lives mainly in the North Atlantic Ocean and the Arctic Ocean, for the first time. Genome mapping allows us to understand the sequence and position of genes on the DNA chain and is essential for obtaining detailed information on which mechanisms allow an organism to survive, develop and reproduce.

The DNA of the Greenland Shark

Identifying the entire genome sequence of the Greenland shark, which inhabits the depths of the North Atlantic and Arctic Oceans, therefore represents a privileged opportunity to understand the secrets that allow its exceptional longevity. Only a few complex animals live longer than humans. Surprising examples are giant tortoises, such as Jonathan, a 191-year-old specimen currently residing on St. Helena, but this record pales in comparison to that of the Greenland shark. Its genetic code is twice as long as that of a human being and is one of the largest animal genome sequences studied to date, with its 6.5 billion base pairs (the record is held by the lungfish, with 35 billion base pairs).

“The enormous size of the Greenland shark genome is mainly due to the presence of repetitive and often self-replicating elements,” explains Professor Alessandro Cellerino, a neurobiologist at the Fritz Lipmann Institute on Aging and the Biology Laboratory of the Scuola Normale Superiore in Pisa, who also participated in the work with the research of a doctoral student in Neuroscience, Davide Drago, specialized in the comparative study of brain aging in sharks. “These transposable elements, sometimes called jumping genes or selfish genes and often considered genomic parasites, represent over 70% of this animal’s genome. A high content of repetitions is often considered harmful because jumping genes can damage DNA and corrupt the genome sequence. In the case of the Greenland shark, however, this does not appear to happen.”

The Secret of Longevity

In contrast, Cellerino and his colleagues, including Arne Sahm of the Fritz Lipmann Institute on Aging, first author of the study, suspect that the expansion of transposable elements may have even contributed to the extreme longevity of the Greenland shark. Many duplicated genes are involved in repairing DNA damage. “In each of our cells, DNA is damaged thousands of times every day and specialized molecular mechanisms constantly repair it. A remarkable finding from comparative genomic studies is that long-lived mammalian species are exceptionally efficient at repairing their DNA,” Cellerino explains. The results on the Greenland shark genome seem to indicate that the expansion of transposable elements may have even contributed to its extreme longevity, as some of these elements ‘kidnapped’ DNA repair genes during their duplication, which were then also duplicated.”

The team also discovered a specific alteration in the protein p53, also known as the “guardian of the genome.” This protein is widely studied because it acts as a control center that coordinates the response to DNA damage in humans and many other species. “This protein is mutated in about half of all human tumors and is the most important tumor suppressor mechanism we know of. Therefore, it is an essential gene for longevity,” says Steve Hoffmann, a biologist at the Fritz Lipmann Institute on Aging. “However, further studies are needed to understand whether and how the observed changes in the sequences of these critical genes promote their protective function and contribute to the exceptional longevity of these animals.”

Genome sequence online

The results of the study and the genome sequence are now accessible to all thanks to the publication on bioRxiv, a disciplinary archive dedicated to the timely sharing of data and research results before publication in a peer-reviewed journal. Sharing via pre-print and the inclusion in this phase in the institutional archive Iris is part of the practices of open science, or the dissemination and reuse of research, which the Scuola Normale has also been pursuing for some time by making the data on its research accessible to the international community of scholars and all interested parties, with a consequent cultural and socio-economic impact on society.

In this case, the genome sequence and the corresponding web resources provided by the research team – which also includes scholars from the Institute of Biophysics of the CNR, the Ruhr University of Bochum, the University of Copenhagen, the University of Genoa and the Stazione Zoologica Anton Dohrn in Naples – will allow researchers around the world to analyze the version of the genes of the Greenland shark of their interest.