Gadusol: Nature's sunscreen

UNIVERISTY OF UTAH RELEASE

Media contacts:

--James Gagnon, assistant professor, School of Biological Sciences, University of Utah, james.gagnon@utah.edu 508-736-9587

--Brian Maffly, research communications, University of Utah Communications, brian.maffly@utah.edu 801-573-2382 

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Humans aren’t the only species that have to worry about exposure to the sun’s ultraviolet rays. Many creatures use sunscreen, just not the white lotions that humans are familiar with. Their sunblock, a compound known as gadusol, is encoded in their DNA.

University of Utah biologist James Gagnon’s lab has studied gadusol production in fish for years, resulting in a new paper demonstrating how females excrete the compound on their eggs. The gadusol molecule was discovered in fish more than 40 years ago, and was originally thought to come from dietary sources. It has since been proven that gadusol is produced from metabolic pathways within the fish.

With help from colleagues in the School of Biological Sciences and Department of Human Genetics,  PhD student Marlen Rice is the lead author of the paper published June 26 in Current Biology. Gagnon, an assistant professor of biology, is listed as the senior author.

Nearly all life on Earth depends on the sun, whether it’s tapping its energy to produce food, or consuming other organisms. But exposure to ultraviolet radiation (UVR) comes at a cost. Wavelengths in UVB rays are especially dangerous, causing damage at a molecular level and leading to mutations in DNA. Excessive levels of UVR exposure can even kill cells, a process known as apoptosis, resulting in what we know as a sunburn. Even in the water, organisms are not safe because biologically harmful levels of UVB can penetrate more than 10 meters deep.

Protection lies in sunscreens which absorb UV photons before they penetrate vulnerable cells and dissipate this absorbed energy as less harmful heat, according to Rice and Gagnon’s paper. They act as physical shields over precious genetic material in cells, preventing damage and mutations.

Organisms across many habitats have developed adaptations, including nocturnal lifestyles and DNA repair mechanisms, to avoid and fix the harm associated with UV exposure. But some have evolved an ability to create their own chemical sunscreens.

“Since sunlit habitats can have significantly nutritive advantages over dark environments and because no repair pathway is completely efficient, many organisms employ sunscreens to avoid UVR damage from occurring in the first place,” the paper said.

Initially, Rice considered melanin as the primary sunscreen in aquatic life.  Melanin is produced in melanophores that migrate to cover parts of the brain and body as fish embryos mature.

To test this hypothesis, Rice altered the genotype in zebrafish to knock out the gene for melanin production.  He found that zebrafish embryos died from UVR exposure at the same rate, regardless of whether or not their genotype was altered. There must be something else protecting the embryos. 

Through CRISPR-Cas9 gene editing, Gagnon’s lab created gadusol-deficient mutant zebrafish to test whether gadusol provide UV protection. Zebrafish were chosen for these experiments because they inhabit sunlit waters, produce gadusol and are amenable to genetic manipulation.

He determined that gadusol is provided for zebrafish embryos by the mother, is the most effective sunscreen over other methods of protection and is lost evolutionarily in fish species when their embryos are not exposed to sunlight.

To show gadusol’s importance, Rice delivered precise doses of UVB to both the wildtype and mutant zebrafish embryos and measured the effect on swim bladder inflation. When exposed to the same dose of UVB, the gadusol-deficient mutant fish were all unable to inflate their swim bladders, indicating that the UV exposure had caused significant developmental defects. This experiment demonstrated that gadusol is critical for the survival of embryonic and larval zebrafish. 

A Boston-based beauty company is looking to synthesize gadusol to create sunscreens that would be safer for both humans and the ocean. For fish, gadusol offers advantages over other sunscreens due to its invisibility. “Transparency as camouflage,” the study said, “is a common trait in aquatic animals, especially in the open ocean where there is nothing to hide behind.”

Melanin’s main drawback is it absorbs most wavelengths in the visible light spectrum as well as the UVB spectrum, so it is detectable by predators. 

 “The environment that they evolved in, which is filled with sunlight and viruses and predators and temperature switches and all this crazy stuff that doesn’t happen in our fish facility,” Gagnon said, “and so if you can bring a little bit of that into our laboratory, now we can apply what’s cool to more questions.” 

The paper,  titled “Gadusol is a maternally provided sunscreen that protects fish embryos from DNA damage,” was funded with a grant from the National Institutes of Health. Other authors include Jordan Little and Julane Muchado, School of Biological Sciences, and Nathan Clark and Jordan Little with the U’s Department of Human Genetics.