It has been known for a number of years that sharks and rays are highly efficient wound healers and suspected to show a greater resistance to cancers—properties that are likely tied to their immune systems, which have been fine-tuned over 400 million years of evolution. Now, a new genomics study of shark DNA by investigators at the Nova Southeastern University (NSU) Save Our Seas Shark Research Center, Guy Harvey Research Institute (GHRI), and the Cornell University College of Veterinary Medicine reveals unique modifications in shark immunity genes that may underlie the rapid wound healing and possibly higher resistance to cancers in these ocean predators.
The findings from this study were published recently in BMC Genomics in an article entitled “Comparative Transcriptomics of Elasmobranchs and Teleosts Highlight Important Processes in Adaptive Immunity and Regional Endothermy.”
“The immune system of sharks and rays has been battle-tested and evolved over hundreds of millions of years,” explained lead study investigator Mahmood Shivji, Ph.D., director of NSU's Save Our Seas Shark Research Center and Guy Harvey Research Institute. “Using genomics approaches to understanding their immunity genesis is likely to produce many more exciting discoveries, some of which could potentially translate into a human medical benefit. Now we have another important reason to make sure we don't lose these marvelous and ecologically critical animals to overfishing, as is currently occurring in many parts of the world. We've just scratched the surface regarding learning what these ancient animals can teach us, as well as possibly provide us in terms of direct biomedical benefits.”
The new study provides the first evidence that some shark and ray immunity genes have undergone evolutionary changes that may be tied to these novel immune system abilities. In particular, the researchers found that two shark immune genes, legumain, and Bag1, stood out. Both these genes have counterparts in humans, where their overexpression is well known to be associated with a whole range of cancers. However, the new research shows that these genes in sharks have become modified and have undergone evolutionary natural selection.
“Several studies have demonstrated antitumor properties of shark-derived compounds in lab studies,” Dr. Shivji noted. “It's intriguing that we are now seeing evidence of evolutionary adaptation in these specific shark immunity genes, which just happen also to be involved in promoting cancer in humans.”
Interestingly, the uniqueness of the shark immune system is even more vast. The shark DNA sequences provide further clues that might explain the rapid wound-healing abilities of sharks while immersed in seawater with its myriads of bacteria, which would be expected to quickly cause infections in open wounds. The researchers found that compared to bony fishes, the four species of sharks and ray examined not only had a much higher proportion of genes involved in antibody-mediated immunity but also that several of the infection immunity-related genes were expressed only in the sharks and rays.
“This higher proportion of genes involved in adaptive (antibody) immunity function could be a key reason behind the infection-fighting and fast wound-healing abilities of sharks and rays,” concluded co-senior study investigator Michael Stanhope, Ph.D., professor in the department of population medicine and diagnostic sciences at the Cornell University College of Veterinary Medicine. “Previous studies of the shark immune system have already yielded some surprises in terms of antibody structure, and these new genetic findings further add to the box of biological novelties in this highly successful vertebrate lineage.”