Huge genome reveals sequence adaptations in key genes for healing and genome stability related to cancer protection – ScienceDaily



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The Great White Shark is one of the most recognized marine creatures on the planet, attracting public fascination and media attention, including one of the most successful films in Hollywood history. This shark has remarkable characteristics, including its massive size (up to 20 feet and 7,000 pounds) and its diving at nearly 4,000 feet deep. Great whites are also a major concern for conservation because of their relatively small numbers in the world's oceans.

In a major scientific step to understand the biology of this iconic top predator and sharks in general, the entire genome of the white shark has now been decoded in detail.

A team led by scientists from the Sharon Research Center of the Save Our Seas Foundation of Nova Southeastern University (NSU) and the Guy Harvey Research Institute (IRSH), the College of Veterinary Medicine of the Cornell University and the Monterey Bay Aquarium completed the white shark genome and compared it to the genomes of a variety of other vertebrates, including the giant whale shark and humans.

The results are reported in the "Latest Articles" section of the journal Proceedings of the National Academy of Sciences.

The decoding of the white shark genome has revealed not only its enormous size – one and a half times the size of the human genome – but also a plethora of genetic modifications that could be the basis of the evolutionary success of the great sharks lived.

The researchers discovered many genes playing important roles in maintaining genome stability – genetic defense mechanisms that neutralize the damage accumulation in the DNA of a species, inducing a molecular adaptation (also known as positive selection) in many genes that play an important role in maintaining genome stability. preserve the integrity of the genome.

These adaptive sequence modifications have been found in genes intimately related to DNA repair, DNA damage response, and DNA damage tolerance, among other genes. . The opposite phenomenon, genome instability, which results from accumulated damage in DNA, is well known to predispose humans to many cancers and age-related diseases.

"Not only was there a surprisingly large number of genome stability genes that contained these adaptive changes, but there was also an enrichment of many of these genes, highlighting the importance of this genetic adjustment in white shark" said Mahmood Shivji, Ph.D., director of the Shark Research Center of the Save Our Seas Foundation of the NSU and the IRSG. Shivji co-directed the study with Michael Stanhope, Ph.D., of the College of Veterinary Medicine at Cornell University.

It should also be noted that the white shark genome contains a very large number of "jumping genes" or transposons, and in this case a specific type, called LINE. In fact, it is one of the highest proportions of LINE (nearly 30%) found in vertebrates to date.

"These LINEs are known to cause genome instability by creating double-strand breaks in DNA," Stanhope said. "It is plausible that this proliferation of LINE in the white shark genome may represent a potent selective agent for the evolution of effective DNA repair mechanisms, and is reflected in the positive selection and distribution of DNA. enrichment of so many genome stability genes. "

The international research team, which also included scientists from California State University, Monterey Bay, Clemson University, the University of Porto, Portugal, and the Theodosius Dobzhansky Center for Bioinformatics of genome, in Russia, also found that many of the same genome stability genes present in white sharks have also been the subject of positive selection and have been enriched by whale shark with huge body and the long life.

The discovery that the whale shark also possessed these essential adaptations of genome stability was significant because, in theory, the risk of cancer was to increase with the number of cells (bulky body) and the lifespan of an organism. – There is statistical support for a positive relationship of body size and cancer risk within a species. Interestingly, this does not tend to fit between species.

Contrary to expectations, very large animals do not contract cancer more often than humans, suggesting that they have acquired superior cancer protection capabilities. The genetic innovations discovered in the genome stability genes in white shark and whale shark could be adaptations facilitating the evolution of their large bodies and their long life span.

"Decoding the white shark genome gives science a new set of keys to solving the lingering mysteries about these dreaded and misunderstood predators – why sharks have thrived for about 500 million years, longer than almost any vertebrate of the planet, "said Dr. Salvador Jorgensen, principal investigator at the Monterey Bay Aquarium, co-author of the study.

But the innovations did not stop there.

Shark genomes have revealed other intriguing evolutionary adaptations in genes related to wound healing pathways. Sharks are known for their extremely fast healing.

"We have found positive selections and gene content enrichments involving several genes related to some of the most fundamental pathways of wound healing, including a key gene for blood clotting," said Stanhope. "These adaptations involving wound healing genes may underlie the much vaunted ability of sharks to effectively heal even large wounds."

The researchers say that they have just explored the "tip of the iceberg" regarding the white shark genome.

"Genome instability is a very important problem in many serious human diseases, and we are now seeing that nature has developed smart strategies to maintain the stability of the genomes of these large and long-lived sharks," he said. Shivji said. "There is still much to learn from these wonders of evolution, including potentially useful information for fighting cancer and age-related diseases, and for improving wound healing treatments at home. the man, as we discover how these animals do it. "

Decoding the white shark genome will also help in the conservation of this shark and related sharks, many of which have rapidly declining populations due to overfishing, "said Steven O. Brien, a conservation geneticist at the NSU, ​​who co-designed this study. " Genome data will be an important asset in understanding the dynamics of white shark populations to better preserve this amazing species that has captured the imagination of so many people. "

This research was funded by the NSU's Save Our Seas Foundation, the Guy Harvey Ocean Foundation, the Hai Stiftung / Shark Foundation, the Monterey Bay Aquarium and the in-kind support of Illumina, Inc. and of Dovetail Genomics.

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