FORGET swimming with dolphins, says marine biologist Woody Hastings, and try it with dinoflagellates. These tiny, alga-like sea creatures seem utterly defenceless. Yet when a hungry predator or curious swimmer comes near, they display their secret weapon-a startling flash of light.
Hastings, from Harvard University, has been studying the colourful performances of bioluminescent creatures for more than 50 years, trying to answer one question: how did the ability to make light evolve? Even Darwin singled out bioluminescence as something his theory of natural selection couldn’t account for. Yet in the ocean it’s commonplace and seems to have evolved independently in many different organisms.
Now a group of Belgian biologists think they have an answer. They’ve discovered that one of the molecules that makes the light show possible had a secret past. As well as helping to explain how bioluminescence evolved, their finding tells a story of the journey of ancient animals deeper into the oceans. It may also hold the secret of how to preserve quite another kind of beauty-youthful skin.
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Different species have their own particular recipes for making light, and glow in a range of brilliant hues from violet through shades of blue, aqua and green to fiery red. Some, like the anglerfish, harbour colonies of bacteria to do the job, but most generate the light for themselves. To produce light, they all require oxygen and two other ingredients. One is called a “luciferin”, from the Latin for “light bearer”. Luciferin molecules react with oxygen incredibly rapidly, burning out almost immediately. As they do so they release energy as photons of light. But the reaction destroys the luciferin, and light produced by a single molecule is too feeble to be visible. So luciferin has a partner to slow it down, an enzyme called luciferase, which binds to oxygen, and coordinates the luciferin reaction so that all the molecules fire off at once, producing a bright flash.
Since luciferase seems to be the key to making the jump to usable light, theories of how bioluminescence evolved generally assume that the enzyme was already in the cell doing something else. And because luciferases react with oxygen, they were thought to have descended from other enzymes with a similar function, called oxygenases. Perhaps they originally evolved to use oxygen in respiration, or in metabolising toxic substances.
“The general view was that the enzyme was the core of the system, and luciferin was just ancillary to it,” says marine biologist Jean-Francois Rees of the Catholic University of Louvain in Belgium. But to him that view didn’t make sense. Luciferases don’t look like oxygenases, and are sluggish in comparison, getting through at most 1600 molecules of oxygen every minute. Oxygenases can deal with up to 40 000 molecules.
Rees turned instead to the most abundant kind of luciferin-a molecule called coelenterazine, which was first isolated from the luminous jellyfish Aequoria victoria. Coelenterazine enables many ocean dwellers to glow in the dark, from exotic tentacled sea gooseberries or frilly pink sea pens to more familiar fish and squid.
Coelenterazine is a simple molecule, composed of just three amino acids joined into a ring, and it had never been seen as much more than an accessory to the all-important enzyme. Most animals that use coelenterazine for bioluminescence can’t make it for themselves. “It’s like a vitamin, they get it from their diets,” explains Rees. Its origin is a mystery, though. “Somebody somewhere in the marine environment is making it,” says Rees. “But nobody knows who.”
Coelenterazine positively devours oxygen. This vigour isn’t necessary for light production, and without the restraining hand of luciferase, coelenterazine would get used up far too quickly. “I thought it must have some other function,” says Rees.
He wondered whether it might have been coelenterazine rather than luciferase that started the bioluminescence ball rolling. Perhaps in a previous life its job was to patrol cells and mop up dangerous relatives of oxygen called free radicals-destructive characters such as superoxide and hydrogen peroxide. Sea water contains large quantities of these molecules, formed when ultraviolet light reacts with oxygen in the water. They are also a by-product of metabolic processes, and are so highly energised that they destroy DNA and cell membranes on contact. For a protective molecule to be able to neutralise them effectively, it would have to work fast.
So Rees and his colleagues set out to test the idea that coelenterazine’s original role in life was to do this. They gave human cells in culture what should have been a fatal dose of free radicals. Then they added coelenterazine, and discovered that even tiny amounts saved the cells from death. Coelenterazine’s special touch is partly a consequence of the molecule being so small. This allows it to penetrate quickly into all compartments of the cell. Better still, when it reacts with oxygen, it forms a by-product that can react again, doubling its effectiveness. This sidekick plays no part in bioluminescence, supporting the idea that coelenterazine once had another role.
That might explain how coelenterazine came to be around in cells, but it doesn’t tell us how it made the jump to producing light. After all, if it was guarding cells against free-radical invaders, every molecule would be needed. A fish couldn’t just drop its defences and start making light for the fun of it.
However, Rees points out that bioluminescence is most common amongst animals in the deep sea. In the darkness, being able to make light has obvious advantages for signalling or startling. The depth may have helped in another way, too. Far beneath the surface, oxygen and its dangerous relatives are scarce because the UV light that generates them cannot penetrate. To cope with the diminished oxygen levels, deep-sea creatures slow their metabolism, and this too means there are fewer free radicals to cope with, as cells aren’t producing them so fast. People thought the lack of oxygen makes the deep ocean a dangerous place to live, says Rees. “But actually it’s a safe place, a refuge from oxidative stress.”
Rees thinks that as animals gradually moved deeper, the lack of light provided increasing pressure for the evolution of bioluminescence at just the time that a diminishing danger from free radicals freed up the ideal molecule for making light. “The conditions were perfect for a shift in function,” he says.
Peter Herring, a marine biologist from the University of Southampton, likes Rees’s theory. “At first this was thought pretty off the wall as an idea. Now people are starting to take him seriously,” Herring says. “It is very difficult to prove what was going on millions of years ago, but Rees has done a great job of coming up with circumstantial evidence.”
Rees has now teamed up with chemists at Louvain University to synthesise a variety of molecules related to coelenterazine, and is testing their ability to neutralise free radicals. The best performer so far is 100 times more efficient than coelenterazine itself, and better than other antioxidants at protecting cells in lab tests, suggesting that it might outperform any current formula used to mop up damaging free radicals in skin exposed to sunlight. The harm done by free radicals is what causes wrinkles and premature ageing of the skin, so ultimately the researchers hope to use the compound in anti-ageing creams.
And coelenterazine may protect against more than just the sun. It might also be useful for treating neurodegenerative diseases such as Alzheimer’s, where dying cells in the brain release free radicals that damage the healthy tissue. Perhaps one day a molecule that brought light to the deep oceans could become a guardian of our mental faculties too.