An international team of scientists from the United States and Europe has successfully sequenced the genome of the great white shark (Carcharodon carcharias) and compared it to the genomes from a variety of other vertebrates.
The great white shark (Carcharodon carcharias). Image credit: Byron Dilkes, Danah Divers.
Sequencing of the great white shark genome revealed not only its huge size — about 1.5 times the size of the human genome — but also genetic changes that could be behind the evolutionary success of these massive creatures.
The team, led by Nova Southeastern University’s Dr. Mahmood Shivji and Dr. Michael Stanhope from the Cornell University College of Veterinary Medicine, found striking occurrences of specific DNA sequence changes indicating molecular adaptation in numerous genes with important roles in maintaining genome stability — the genetic defense mechanisms that counteract the accumulation of damage to a species’ DNA, thereby preserving the integrity of the genome.
These adaptive sequence changes were found in genes intimately tied to DNA repair, DNA damage response, and DNA damage tolerance, among other genes. The opposite phenomenon, genome instability, which results from accumulated DNA damage, is well known to predispose humans to numerous cancers and age-related diseases.
“Not only were there a surprisingly high number of genome stability genes that contained these adaptive changes, but there was also an enrichment of several of these genes, highlighting the importance of this genetic fine-tuning in the white shark,” Dr. Shivji said.
Also notable was that the white shark genome contained a very high number of ‘jumping genes’ or transposons, and in this case a specific type, known as LINEs. In fact this is one of the highest proportions of LINEs (nearly 30%) discovered in vertebrates so far.
“These LINEs are known to cause genome instability by creating double stranded breaks in DNA,” Dr. Stanhope said.
“It’s plausible that this proliferation of LINEs in the white shark genome could represent a strong selective agent for the evolution of efficient DNA repair mechanisms, and is reflected in the positive selection and enrichment of so many genome stability genes.”
The researchers also found that many of the same genome stability genes in the great white shark were also under positive selection and enriched in the huge-bodied, long-lived whale shark (Rhincodon typus).
The discovery that the whale shark also had these key genome stability adaptations was significant because theoretically, the risk of developing cancer should increase with both the number of cells (large bodies) and an organism’s lifespan — there is statistical support for a positive relationship of body size and cancer risk within a species. Interestingly, this does not tend to hold up across species.
Contrary to expectations, very large-bodied animals do not get cancer more often than humans, suggesting they have evolved superior cancer-protective abilities.
The genetic innovations discovered in genome stability genes in the white and whale shark could be adaptations facilitating the evolution of their large bodies and long lifespans.
The shark genomes revealed other intriguing evolutionary adaptations in genes linked to wound healing pathways.
“We found positive selection and gene content enrichments involving several genes tied to some of the most fundamental pathways in wound healing, including in a key blood clotting gene,” Dr. Stanhope said.
“These adaptations involving wound healing genes may underlie the vaunted ability of sharks to heal efficiently from even large wounds.”
The findings appear in the Proceedings of the National Academy of Sciences.
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Mahmood Shivji et al. 2019. Great White Shark Genome. PNAS, in press; doi: 10.1073/pnas. 1819778116
