Scientists during DNA sample taking process in the Arctic region.
Credit: NYT
The Greenland shark is not exactly charismatic. Its hulking frame is covered by sandpaper skin. Its fins, stunted, sit awkwardly along its sides. And its eyes, perpetually cloudy, are often host to wormlike parasites that dangle as the shark slowly roams the depths of the North Atlantic and Arctic oceans.
But looks aside, the species has a surprising capacity: It can live for as long as about 400 years. Now, an international team of scientists from Europe and the United States has mapped the genome of the Greenland shark, offering scientists an opportunity to glean the secret to the shark’s outstanding longevity.
“Any research into the mechanisms of how this animal is able to live for such a long time will at some point need the genome sequence,” said Steve Hoffmann, a computational biologist at the Leibniz Institute on Aging and the Friedrich Schiller University Jena, in Germany, who led the research.
The findings, published as a preprint in bioRxiv, provide a comprehensive assembly of the shark’s genetic makeup. They also provide initial insights into the specific genes and biological mechanisms, including a network of duplicated genes involved in DNA repair, that may be responsible for the shark’s exceptional lifespan.
The scientists found that Greenland sharks possess very large genomes: about 6.5 billion DNA “base pairs,” or building blocks — about twice as many as in humans, and the biggest genome of any other shark sequenced to date.
“We wouldn’t have guessed that it’s so large,” said Arne Sahm, a bioinformatician at the Leibniz Institute on Aging and Ruhr University Bochum, who was the lead author on the study.
Surprisingly, more than two-thirds of the genome was composed of repeated genes known as transposable elements, or jumping genes. These genes insert themselves in others and self-replicate through a copy-and-paste mechanism. In doing so, they often disrupt the normal functioning of genes and may cause mutations, deletions or duplications, which can lead to the development of diseases or developmental issues in the organism.
“These are parasites, genomic parasites,” Hoffmann said. “They have a pretty bad reputation.”
The findings led the researchers to wonder how sharks could live so long if they carried such a high number of these harmful genes. They proposed that the Greenland shark might have evolved a unique way to hijack the machinery of these jumping genes to duplicate genes involved in DNA repair.
“These are animals that live longer than human beings, and they do this in the wild, without medicines or hospitals or health care,” said João Pedro de Magalhães, a molecular biogerontologist at the University of Birmingham in England, who was not involved in the study.
Studying the sharks, he added, may help scientists to one day “develop cancer therapies or prevention measures, or a greater fundamental understanding of cancer that will lead to clinical benefits” in humans.
The shark’s remarkable longevity first came to light in 2016, when a landmark study published in Science used radiocarbon dating methods and modeling techniques to estimate the ages of 28 Greenland sharks.
The researchers found that the oldest sharks could live for about 400 years and reached sexual maturity around age 150.
Flabbergasted, scientists from around the world have since been studying Greenland sharks to better understand how the species can live so long. Some are looking at its heart; others are homing in on its metabolism, and many are monitoring its behavior and ecology.
The pinnacle has been to unravel the Greenland shark’s genome.
In the past five years, at least three teams have been racing to produce a full genome of the shark.
Hoffmann and his collaborators were the first to publish the shark’s genome, which covers around 92% of its entire DNA.
“We knew nothing before about its genome, and now we have a complete genome sequence,” said Steven Austad, a biologist at the University of Alabama at Birmingham, who was not involved in the study. “I think that’s great.”
Reaching this stage took extensive fieldwork, including several expeditions off the coasts of Greenland, where members of the team caught Greenland sharks, euthanized them and took tissue samples from their spinal cords.
Those tissue samples were then stored at low temperatures and sent to the Leibniz Institute, where the DNA was extracted, sequenced and compared with that of other sharks. In the end, the team sequenced the DNA from brain tissue from one shark.
A key finding identified a network of 81 genes that were found only in Greenland sharks and that played a role in DNA repair.
The researchers hypothesized that regular DNA repair genes had evolved to exploit the machinery of jumping genes in order to copy and paste more of themselves. That process may have helped them to both counteract the accumulated damage caused by jumping genes and improve the shark’s DNA repair abilities.
At the center of this network was a well-known gene, called TP53, that has been implicated in DNA repair and tumor suppression<em>. </em>A study published in 2016 showed that elephants carried 20 copies of this gene, and scientists believe that the gene may account for the animal’s strong resistance to cancer. The gene was also found to be structurally altered in Greenland sharks, although the team is still assessing whether this change would enhance the shark’s longevity.
The shark results are interesting, Austad said, but he cautioned that duplications don’t always reveal much. “Lots of genes get duplicated and don’t have any particular consequence,” he said.
He added that researchers would need to understand how these findings apply to live cells of different types, an effort that could entail culturing Greenland shark cells, converting them into stem cells and differentiating them into, say, heart or brain cells.
“Then you could tinker — then you could manipulate the genome,” Austad said.
Sahm said his team hoped to conduct genome sequences of species that are shorter-lived but evolutionarily very similar to Greenland sharks, like the Pacific sleeper shark. That also might shed light on what enables Greenland sharks to live so long.
Whichever direction the research takes, Austad said, it’s an exciting time for Greenland shark research.
“Now is where the fun begins,” he said. “Now that we have the genome, it’s a question of developing hypotheses and then testing them.”