New international Monash University-led research has explained the reasons for and implications of low cancer rates in sharks, which until now have remained a decades long mystery.
In a world-first collaborative international study, co-led by Monash University’s Australian Regenerative Medicine Institute (ARMI), with researchers from Germany, Sweden and the USA, scientists have discovered that sharks possess the lowest level of mutation between generations of any vertebrate species (animals with a backbone) to date.
This low level of mutation may be the key to explaining why they are less likely to develop cancers. While this may sound like good news for sharks, it turns out to be a double-edged sword.
Mutations are critical as they generate genetic variability within populations, facilitating the ability to adapt to new conditions and enabling evolutionary change. With sharks evolving very slowly, this puts them at risk of being unable to withstand ecological pressures such as overfishing and habitat loss.
The research, published in Nature Communications, highlights the urgent need to prioritise preservation of the remaining genetic diversity of global shark populations.
The study established the first ‘laboratory’ shark model using the epaulette shark, a small species found north-east of Australia. This surprisingly resilient shark can walk for up to 30 metres on land using paddle shaped fins and survive without oxygen for up to two hours, attributes that made them an ideal candidate for a captive breeding program at ARMI.
“Our development of breeding and pair mating protocols for epaulette sharks enabled us, for the first time, to genetically evaluate the mutation rate within a shark pedigree,” explained ARMI Director of Research and co-senior author, Professor Peter Currie.
Using the newly established shark model, the international research team generated a high-quality reference genome, and re-sequenced the entire genome of parents and nine offspring to detect new mutations.
“We estimate a mutation rate of 7×10−10 per base pair of DNA, per generation in epaulette sharks, which is the lowest mutation rate recorded to date for any vertebrate species,” Professor Currie said.
“This suggests that sharks may have a lower capacity to survive a drastic fall in population numbers compared to other species. Until now, sharks had not been included in mutation rate research of vertebrates despite the important role they played in a diverse range of marine ecosystems.
“It can also explain low cancer rates in shark species, as the mutation rates that generate cancers would be expected to be low in sharks, given they are linked to the inherited mutation rate.
“We therefore hope that this study will provide the evidence required to end the pointless harvesting of shark species for the production of baseless dietary supplements that give false hope to cancer sufferers.
"The next step for our research is to understand what is unique about the biology of sharks that leads to this low rate of mutation, knowledge that may lead to an ability to slow mutation rates in our own tissues and lower cancer incidence.”
Up to 72 million sharks are killed annually by the fin trade, with many targeted species facing the threat of extinction. Many more sharks are harvested for cartilage extracts used in dietary supplements for cancer treatments, and sharks are often caught inadvertently in fisheries directed at other species.
Joint first author Dr Frank Tulenko, an ARMI research fellow, said mutations were fundamental to evolution because they generated variability within populations, enabling evolutionary change.
“The mutation rate is a crucial parameter for many calculations and predictive modelling in the fields of ecology and evolution, genetics and genomics,” Dr Tulenko said. “The rate of mutation provides an indication of a species’ ability to generate diversity, with a low rate of intergenerational mutations indicative of a reduced ability to respond to a sudden drop in population numbers.”
Professor Currie said the extremely low mutation rates could hamper efforts to restore shark populations and genetic diversity.
“We know that sharks are particularly sensitive to unsustainable fishing practices and rapid changes in habitats,” Professor Currie said. “Now we also know that sharks evolve slowly, which means they are less able to counteract the mounting ecological threats they face.
“As sharks play fundamental roles in a diverse range of marine ecosystems, it is critical that we support conservation efforts to preserve the genetic variation within shark populations and to protect shark species more broadly.”
This study was jointly led by:
Team Lead Australia, Professor Peter Currie, Australian Regenerative Medicine Institute, Monash University. Contact: peter.currie@monash.edu
Team Lead Germany: Professor Manfred Schartl, University of Würzburg.
Contact: phch1@biozentrum.uni-wuerzburg.de
Team Lead Sweden: Professor Leif Andersson, Uppsala University.
Contact: leif.andersson@imbim.uu.se
Team Lead USA, Professor Shawn Burgess, National Institutes of Health.
Contact: burgess@mail.nih.gov
About The Australian Regenerative Medicine Institute at Monash University
The Australian Regenerative Medicine Institute is one of the largest regenerative medicine and stem cell research organisations globally and Australia’s only research institute specialising in regeneration and stem cells. Located on the Clayton campus of Monash University, researchers at ARMI focus on understanding the basic mechanisms of the regenerative process, aiming to eventually enable doctors to prevent, halt and reverse damage to vital organs due to disease, injury or genetic conditions. Website: https://www.armi.org.au/
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