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Sharks’ Low Mutation Rate a Cancer Shield but a Survival Challenge

An Epaulette Shark crawls along an aquarium.
Credit: David Clode / Unsplash.
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Despite occupying oceans for ~400–500 million years, sharks haven’t really changed all that much. This basal group of vertebrates are generally considered to be a “slow-evolving” lineage, but existing data analyzing shark evolution over time isn’t exactly plentiful.

Considering the ecological burdens that this species currently face, including habitat loss and overfishing, studying sharks’ adaptive potential rate is essential for their preservation.

In Nature Communications, a collaborative team of scientists, coordinated by researchers at the Julius Maximilian University of Würzburg (JMU), published a high-quality reference genome for the epaulette shark (Hemiscyllium ocellatum). The epaulette is often nicknamed the “walking shark” as it uses its fins to “walk” between coral reefs.

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“We sought to establish the epaulette shark as a laboratory model system and generate a high-quality, haplotype-resolved reference genome. We could then use this resource to estimate the de novo mutation rate for a shark species,” the authors write. “The epaulette shark was chosen for this purpose because of the possibility of performing captive breeding and thereby ensuring a full-sib family for whole genome resequencing.”

Record-low mutation rate in vertebrates  

The research team, led by Senior Professor Manfred Schartl at the Department of Developmental Biochemistry at JMU, caught epaulette sharks off the northeast coast of Australia and set up a breeding station at the Australian Regenerative Medicine Institute (ARMI) at Monash University.

Schartl and colleagues obtained genome sequencing data for the parents and nine of their offspring, allowing them to analyze the rate of de novo mutations.

What are de novo mutations?

A de novo mutation is a germline mutation that occurs within one generation, i.e., the alteration to the genome was not inherited from an organism’s parents – it occurs spontaneously.

With a mutation rate of ~7×10-10 per base pair per generation, epaulette sharks have the lowest mutation rate recorded in vertebrates to date, the study shows. “The estimated mutation rate is 17-fold lower than in humans and an order of magnitude lower than the slowest evolving mammal recorded to date,” Schartl and team describe.

Previous notions that sharks are not susceptible to cancer due to the high amounts of cartilage found in their bodies have been debunked as “pseudoscience” and a potential threat to the species. Purified shark cartilage has been tested in human clinical trials and, while no harmful side effects were reported, it was not found to prolong life. While not resistant to the disease, sharks are suggested to have a lower cancer rate than other vertebrates. "The low mutation rate could play a decisive role in this," explains Schartl, as most cancers are caused by spontaneous or induced somatic mutations.

A lower mutation rate might prove beneficial for cancer protection, but it comes at a cost: de novo mutations enable a species to adapt over time in response to changing environmental conditions.

“Extrapolating our findings to other shark species that lack the population size stability evident in epaulette sharks suggests a similar low mutation rate may result in long-term negative effects of population bottlenecks in already endangered and overfished species,” Schartl and team explain. “Our study, therefore, provides compelling evidence for the need to prioritise preservation of the remaining genetic diversity of global shark populations.”

Reference: Sendell-Price AT, Tulenko FJ, Pettersson M, et al. Low mutation rate in epaulette sharks is consistent with a slow rate of evolution in sharks. Nat Comms. 2023;14(1):6628. doi: 10.1038/s41467-023-42238-x

This article is a rework of a press release issued by the Julius Maximilian University of Würzburg.