Inner Workings: Can single molecules bind together entire ecosystems?

Off the coast of California, puffy slug-like creatures—named sea hares (Aplysia californica) for their bunny ear-like tentacles—chomp their way across underwater fields of red-brown algae. The algae produce mycosporine-like amino acids (MAAs), chemicals that give the sea hares their murky maroon hues. The animals deploy these same molecules for defense. When faced with predators such as starfish or lobsters, sea hares puff out purple clouds of MAA-loaded ink mixed with opaline, a milky-white fluid; the chemicals deter enemies and warn neighboring sea hares to race to safety.

California sea hares like this one get MAA from the algae they eat; some researchers label the compound a keystone molecule for the multiple roles it plays throughout the ecosystem. Image courtesy of Kevin Lee (photographer).

As they studied these interactions, Charles Derby of Georgia State University and his colleagues realized that the myriad messages conveyed by MAAs rippled across many levels of the community, from plants to sea hares to apex predators, such as starfish (1). To Derby, this role qualified MAAs for an intriguing concept: certain molecules could have surprisingly large impacts on multiple levels in ecosystems, even when they were only present in tiny concentrations (2).

“What started off as a single compound made by one species has effects that reverberate throughout a food web at different trophic levels,” says ecologist Richard Zimmer of the University of California, Los Angeles, who developed this idea of “keystone molecules.” “So this one molecule punches in with effects that are far greater than originally intended,” he says.

In 2013, Zimmer and his then-graduate student Ryan Ferrer borrowed a concept from ecology and dubbed such chemicals “molecules of keystone significance” (3). Although the notion that molecular signals can guide multiple ecological interactions isn’t novel, understanding the undue influence of a relatively rare chemicals could offer an important way to understand how different communities function, says Derby.

By looking at ecosystems through a chemical lens, researchers could identify a “suite of new species that are fundamentally important to maintaining the natural structure of a community simply because of the molecules they make,” says Zimmer.

In the long run, identifying keystone molecules could prove crucial to improving ecosystem management or conserving habitats, perhaps by introducing or removing specific chemicals that influence animal behavior. Like Derby, many ecologists have begun to embrace the idea. But just how useful this concept will be remains uncertain. And the definition of what makes a keystone molecule—and how to spot or classify a chemical as one—could shift as the concept is put to field tests. “Ecologists have wrestled with the idea of how keystones should be identified and determined, and I think it’s the same here,” Zimmer says.

From Species to Molecules

In the 1960s, just a few miles north of sea hare habitats, ecologist Robert Paine once spent months prying predatory starfish (Pisaster ochraceus) off rocks with a crowbar to assess how starfish shaped their communities. Paine’s landmark experiments led him to propose the idea that certain organisms, which he dubbed “keystone species,” influenced ecosystems far more than one might expect based on their relative abundance (4).

When extending the concept to chemicals, Zimmer and Ferrer focused on studies of neurochemicals such as tetrodotoxin, a potent toxin produced by pufferfish and other species. More recently, a study of cuticle proteins in barnacles suggests a glycoprotein that helps larvae migrate and attach to rocks is also exploited by barnacle predators. “So this single compound simultaneously drives opposing demographic processes,” says Zimmer (5).

Echoing Paine’s experiments, Ferrer, who is now an associate professor at Seattle Pacific University, has tested the possibility that saxitoxin, a neurotoxin produced by algae that accumulates in mussels, is a keystone molecule. In Puget Sound, Ferrer and his students assessed how saxitoxin affects P. ochraceus, Paine’s archetypal keystone species. Ferrer and his students tracked saxitoxin during and after algal blooms, recorded the force needed to remove a starfish from rocks, and found the weakest forces were needed when saxitoxin levels were at their highest during a bloom. In laboratory experiments, the toxin also altered starfish reproductive success, but didn’t appear to affect which mussels became starfish food (6).

But unlike predatory starfish, saxitoxin levels in an environment can spike and ebb within days. “It may be undetectable at one time and really high days later, so what we’re looking at is a relative abundance,” Ferrer says. “One of the biggest challenges we faced was to pin it down quantitatively.”

Precisely why a single molecule and its derivatives may be co-opted by algae, herbivores, and predators for disparate functions is still a mystery. One reason, Derby suggests, is that such specialized molecules are energy-intensive to create. “It might be more efficient to repurpose the same molecules,” he says.

The parent molecule in paralytic shellfish toxins, saxitoxin (STX), functions as a neuroinhibitor in coastal marine communities, affecting prey distribution. (A) STX has inhibitory effects (broken arrows) and stimulatory responses (solid arrows) via primary producers (1P) and consumers (C). Dinoflagellate cysts generate harmful algal blooms (B) that release STX into coastal water, where invertebrates such as shellfish (C) retain the toxin, making them risky meals. Shorebirds (D) flee algal blooms and opt for nontoxic prey. STX triggers prey switching in keystone species, such as sea otters (E). (A) Reproduced from ref. 3, with permission from Oxford University Press. Images courtesy of photographers (B) Don Anderson, (C) Jonathan Ho, (D) Marlin Harms, and (E) Donald Quintana.

Ripple Effects

Nonetheless, identifying whether something is in fact a keystone molecule can prove tricky. Although both Zimmer and Ferrer have conducted field experiments, it’s difficult to eliminate a chemical from an ecosystem, so parallels to Paine’s starfish experiments are nearly impossible. “You can’t do the experiment where you take it out of a food web and see what happens,” says Gabrielle Nevitt of the University of California, Davis.

Nevitt adds that with further studies, the chemical background of a keystone cue may prove to be just as important as the individual molecule itself. “It’s an attractive idea, but I think there’s more complexity to it than just one molecule,” she says. “But ideas like this are the platform for further experimentation.”

Most molecules identified as keystones thus far appear to exert neurological effects that alter the behavior of species at multiple levels of ecosystems. If, for example, a molecule has an impact on an apex predator such as a starfish, the result may be increased predation, the migration of a foundation species such as barnacles, or the proliferation of an invasive species.

As keystone molecules emerge from experiments that elucidate a chemical’s many roles, Ferrer suggests they could have practical benefits. For example, the saxitoxin-producing algae that cause toxic blooms can hamper shellfish operations or fisheries. “Removing or suppressing algal blooms might be economically beneficial, but could have far-reaching impacts on the ecosystem,” he says.

Considering chemistry could help assess the impact of nonnative species introduced to an ecosystem, or help to identify conservation strategies and priorities for endangered or threatened species. “Whether or not they get a particular designation could hinge on whether or not the species plays a central role in metabolizing a keystone molecule,” Ferrer adds.

Much work remains before such uses become a reality. Still, Derby calls keystone molecules a “neat organizing concept.” “It challenges some of the concepts of what shapes community structure,” he says, “and makes us think in ways that we haven’t before.”