Genome of shark that lives up to 500 years may reveal secrets of longevity

The Greenland shark is known for being elusive, effectively hiding its most surprising features for years. The slow-moving creatures primarily inhabit the deep, cold waters of the North Atlantic and Arctic Ocean, and are the only sharks capable of withstanding freezing temperatures year-round. Some individuals of the species may have been swimming there since colonial times — and researchers are just beginning to figure out how.

Due to the marine animal’s slow metabolism, scientists have long suspected that the Greenland shark was exceptionally long-lived, but there was no way to determine the exact magnitude until recently. Research published in 2016 determined that sharks are the longest-lived vertebrates, likely living for around 400 years, with estimates ranging from 272 to over 500 years. Now, a different study aims to understand the mechanism behind this longevity.

An international team of scientists has become the first to map the Greenland shark’s genome, sequencing about 92% of its DNA and providing insights into the inner workings of the long-lived fish. The assembly, the computational representation of their genome, not only adds to what is known about the structure of sharks and how their bodies work, but also provides clues about why the animals have such staying power, the researchers said.

“Only by assembling the genome can we really understand what mutations, for example, accumulated in the shark that led to this enormous longevity,” said Steve Hoffman, author of the new research on the Greenland shark and a computational biologist at the Leibniz Institute. on Aging in Germany. “To that end, this genome is a kind of tool, if you will, that allows us, and of course other researchers as well, to look at these molecular mechanisms of longevity.”

The study authors released their findings as a pre-print — a scientific paper that did not go through the peer review process — while inviting more scientists to study the genome and conduct their own analyzes of the shark’s DNA, Hoffman said.

There are few species of animals that live longer than humans, particularly compared to our weight and body size. By studying the Greenland shark’s longevity mechanisms, scientists could also gain more insights into how to potentially extend human lifespan, the authors said.

Greenland shark genome

Greenland sharks grow at an extremely slow rate of less than 1 centimeter per year, but they can eventually reach more than 6 meters in length, and they do not reach sexual maturity until they are more than a century old. It is suspected that the oldest of the species may survive for more than half a millennium.

The study authors found that the shark genome is extraordinarily large, twice the size of a human and larger than any other shark genome sequenced to date. Researchers are analyzing the genome to explore what its large size could mean for the shark’s longevity.

One reason for a longer genome may be related to the shark’s ability to repair its DNA, a trait commonly seen in other species with exceptional longevity, including the naked mole rat, the longest-lived rodent that lives to 30 years or more. and certain species of turtles that can live more than 100 years.

The Greenland shark is unique in that a large amount — more than 70% — of its genome is made up of jumping genes, which can move within the DNA sequence by duplicating themselves, sometimes creating mutations. Often, these duplications are referred to as genetic parasites due to their potential harmful effects, including genetic diseases such as cancer.

However, it appears that in the Greenland shark, genes that repair DNA have acted as jumping genes, distributing themselves throughout the genome and slowing down the aging process by repairing damaged DNA. As a result, “the detrimental effect of these transposable elements (jumping genes) is not only cancelled, but perhaps even reversed, so that genome integrity is even better in the Greenland shark,” said lead author Dr. Arne Sahm , bioinformatician and junior professor at Ruhr University Bochum in Germany.

The authors suggest that DNA repair genes in species at some point evolved the ability to multiply, further contributing to DNA repair and, consequently, longevity. Researchers want to further explore and analyze the Greenland shark’s DNA, comparing its genome to other species of sharks and shorter-lived fish, to provide additional evidence for this unique trait, Hoffman said.

Studying the Greenland shark

Before researchers sequenced the Greenland shark genome, only about 10 genomes were available for all elasmobranchs — a subclass of fish that includes sharks, rays and rays — said Dr. Nicole Phillips, associate professor of ecology and biology organismic studies at the University of Southern Mississippi in Hattiesburg. Phillips was not involved in the research conducted by Hoffman, Sahm and their team.

“The more high-quality genomes that are sequenced, the better we can understand the genetic basis of the shared and unique characteristics of this ancestral group,” Phillips said in an email. “Identifying the genetic basis of longevity in different species, including long-lived sharks, allows researchers to understand the biology of aging and longevity.”

Due to sharks’ preference for deep waters, historically most information about the Greenland shark came from commercial fishing records. Over the past decade, researchers have increasingly used video, including remotely operated vehicles and baited cameras, as well as observations on captured specimens to research the elusive shark.

To sequence and study the shark’s genetic makeup, the authors euthanized several specimens to obtain tissue samples, for which they had a research permit. But scientists hope their work on the Greenland shark genome will help conserve the species, Hoffman said. The Greenland shark is currently listed as vulnerable on the International Union for Conservation of Nature’s Red List of Threatened Species, with its last assessment in June 2019.

“The authors were able to gain insights into an animal that truly occupies a unique place in the evolutionary tree of life. It’s very ancestral and so it could basically represent, at least in sharks, potentially how all genomes evolved, because it provides this snapshot of a really interesting, very specialized genome,” said Dr. Toby Daly-Engel, associate professor of engineering oceanic and marine sciences at the Florida Institute of Technology in Melbourne and director of the Shark Conservation Laboratory at Florida Tech. Daly-Engel was not involved in the research.

“On the one hand, I think the insight into these jumping genes is really interesting, and on the other hand, it’s not surprising that they’re seeing things we’ve never seen before,” he added, “because even though we’ve sequenced other shark genomes, the species of sharks are so different from each other that we can expect new things with each species.”

Extending human life

In previous research, scientists have been able to extend the lifespan of certain short-lived species, such as flies and mice, using genetic modifications. By researching more long-lived species, scientists can gain a better understanding of the aging process for all species and the tools that could potentially be applied to extend human lifespan, Sahm said.

“Evolution does not always choose the same path. So if, say, the goal is to have better DNA repair, but that can be achieved by multiple mechanisms, and the mechanisms are different in mole rats and whales and sharks, we need to learn about all of them and then see which ones we can maybe adapt more easily for human use,” said Dr. Vera Gorbunova, a professor of medicine and biology at the University of Rochester in New York and lead author of a 2023 study that used genes transferred from naked mole rats to extend lifespan. of mice. Gorbunova was not involved in Greenland shark research.

“Once researchers understand the mechanism… then we can see if we can develop a specific drug to target this enzyme in the genome in this way,” he added. “You can dream about gene therapy, maybe we can give people a Greenland shark gene, but that might be more of a science fiction kind of approach, but something more readily translatable would be, well, maybe we can develop a drug that targets a human gene and make it function a little more like a Greenland shark. And that… would improve DNA repair in humans.”

There are many environmental influences that damage human DNA, such as sunlight or smoking. By learning more about the Greenland shark’s unique DNA repair technique, scientists can begin to study how this trait contributes to other factors slowing aging, such as the suppression of tumors in Greenland shark cells, as well as possible effects on the cells of other species, including our own, Sahm said.

“If we really want to significantly increase human lifespan, or perhaps even better, extend the percentage of our lifespan in which we are actually healthy, fit and can do things… it’s good to watch the tricks of very long-lived animals,” he added , “how they change their system as a whole, what strategies they use and then learn from… those strategies.”

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This content was originally published in Genome of shark that lives up to 500 years may reveal secrets of longevity on the CNN Brasil website.

Source: CNN Brasil

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