Gadusol: A More “E-fish-ent” Sunscreen

As temperatures rise, and outside activities become more popular, many people are thinking about protecting themselves from sunburns and melanomas, primarily using sunscreen.

Marlen Rice. Banner Image: Jamie Gagnon and Marlen Rice. Credit: Todd Anderson

However, humans aren’t the only species that have to worry about UV damage. Many species use sunscreen, but not the white lotions that humans are familiar with. Their sunscreens are coded in their DNA. The recently published paper: “Gadusol is a maternally provided sunscreen that protects fish embryos from DNA damage” is the culmination of years of research by University of Utah School of Biological Sciences graduate student Marlen Rice and Assistant Professor of Biology Jamie Gagnon. 

Gadusol is a chemical sunscreen that is found in the eggs of many fish species. The molecule was discovered in fish over 40 years ago, and was originally thought to come from dietary sources, but it has since been proven that gadusol is produced from a sugar intermediate in one of the metabolic pathways within the fish. The mother deposits the chemical into her eggs as she lays them to protect her babies from the sun. 

Rice grew up on a farm an hour south of Salt Lake, and attended Utah State University where he received a bachelor’s degree in molecular biology. He has always been interested in how animals develop in relation to the world around them. Rice says “The fun thing to me about biology is just the fact that [living] things are dynamic and they interact [with] their environment… I like thinking about animals in relation to ecology. I want to try to bridge those two gaps — the molecular field with ecology.” Rice’s lifelong passion for animals and his industry background inspired him to use laboratory tools to investigate ecological factors, starting with the sun.

UVR Exposure

Nearly all life on Earth has an important relationship with the sun, whether that be by using the energy from it to produce food, or consuming other organisms who do. This comes with the cost of extensive exposure to ultraviolet radiation (UVR). UVB rays are the specific wavelengths that are especially dangerous to living organisms. UVR damages proteins and DNA on a molecular level. This damage leads to mutations in DNA, and excessive levels of UVR exposure can even induce apoptosis or cell death, producing what we know as a sunburn. 

According to the paper, “[s]unscreens absorb UV photons before they penetrate vulnerable cells and dissipate this absorbed energy as less harmful heat.” Sunscreens act as physical shields over precious genetic material in cells, preventing damage and mutations. Even in the water, not all aquatic organisms are safe from UVR exposure because biologically harmful levels of UVB can penetrate over 10m deep in clear water. Organisms across many habitats have developed adaptations including nocturnal lifestyles and DNA repair mechanisms to help avoid and fix the problems associated with UV exposure. Furthermore, “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.” 

Initially, Rice only looked at melanin as the primary sunscreen in aquatic life. In fish, melanin is produced in melanophores that migrate to cover aspects of the brain and body as the fish matures. What he found was that zebrafish embryos were dying from UVR exposure at the same rate, regardless of whether or not their genotype was altered to knockout the gene for melanin production. It became clear that there was something else protecting the embryos. 

Zebrafish

Two-day-old zebrafish. Credit: Marlen Rice

Rice created gadusol-deficient mutant zebrafish through CRISPR-Cas9 gene editing to test gadusol as a sunscreen. Zebrafish were chosen for these experiments because they naturally live in 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 exposed to UVR. 

Fish have been benefiting from gadusol for eons, but in the future, humans could too. Gadusol Laboratories, started at Oregon State University, has been acquired by Boston-based beauty company Arcaea. Their research focuses on synthetically producing gadusol to create sunscreens that would be safer for both humans and the ocean. 

For fish, gadusol offers a tremendous advantage over other sunscreens due to its invisibility. “Transparency as camouflage,” they write, “is a common trait in aquatic animals, especially in the open ocean where there is nothing to hide behind.” This is one of the largest drawbacks for melanin: since it absorbs most wavelengths in the visible light spectrum as well as the UVB spectrum, it is detectable by predators. 

The Beauty of DNA

The sun is just one of the unique ecological challenges that aquatic ecosystems pose to their inhabitants. Gagnon says, “you sort of forget they actually evolve out in the world, [a] very challenging world full of pressures on their survival. …  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, and so if you can bring a little bit of that into our laboratory, now we can apply what’s cool to more questions.” 

These environmental factors will inspire their research with zebrafish moving forward. Rice is also curious about the evolutionary history of gadusol itself. He says, “I’d really like to fill out on the tree of life how widespread gadusol is. And another thing I’m really interested in thinking about is, it seems like at some point, land vertebrates stopped using gadusol. I think evolutionarily it’d be really interesting to think about that. At what point did they move away?”

The answers to these mysteries lie within — within DNA to be specific. Rice says “I really do love the idea of DNA. I think it’s a really beautiful thing … . The fact that it’s an unbroken chain of DNA replication and now lives inside of you.” It will be the combination of molecular biology tools and ecological inspiration that translates the evolutionary history written into the genetic code for all living organisms. 

By Lauren Wigod

Read a first-person account from a zebrafish in Animals of the U: Zippy the Zebrafish.