A New, Chemical View of Ecosystems

The biological world is awash in chemical signals. Ants lead their nest mates to food with winding trails of pheromones, plants exude aerosols to warn their neighbors of herbivores, and everything you experience as “smell” is a molecule latching onto your nose. Some molecular messages find their targets; most linger unread in the environment. But sometimes, other species — chemical eavesdroppers, bystanders or visitors — can pick up and interpret the signals in their own way. If the message is powerful enough, the impact can ripple out across an ecosystem.

In 2007, biologists named these potent molecules after a popular concept in ecology. “Keystone species,” such as starfish in Pacific Northwest tidepools, aren’t abundant, but they have outsize effects on the food web — making those species as crucial to their ecosystems as a load-bearing keystone in an archway. If they’re removed, the idea goes, the entire ecosystem could collapse into a different form. “Keystone molecules,” then, are rare chemicals that can structure, shape and alter connections between species across entire ecosystems.

It was a promising idea, but hard to nail down empirically. Chemical actors are difficult to detect and measure in a complex setting such as an ecosystem. Add to that a need to trace their effects and interactions through a variety of organisms, and you end up with a tangled experiment that demands many kinds of scientific expertise.

Now, a comprehensive study published in Science Advances has combined field work, chemical analysis and community ecology to lend fresh support to the keystone molecule theory. Researchers studying pungent Alderia sea slugs in a California mudflat isolated molecules new to science from their unappetizing slime. As the scientists studied this cocktail and later introduced it to the mudflat, they recorded profound effects on other species and on the overall nature of the habitat.

“One small, simple molecule can be tying together these seemingly unrelated species and whole ecosystem processes,” said study author Patrick Krug, a marine biologist at California State University, Los Angeles. “It is now being recognized as this general phenomenon that we’ve just been kind of oblivious to.”

The study took “herculean effort,” said the chemical ecologist Richard Zimmer from the University of California, Los Angeles, who coined the term “keystone molecule.” “Krug’s group did absolutely first-rate chemistry combined with behavioral ecology. It’s great to see, after 17 years, that Krug’s group picked up our original concept and did a pretty darn bang-up job testing the theory of keystone molecules.”

Ecology has historically overlooked chemical interactions in food webs. “That could be a big oversight,” Krug said. “If chemicals diffusing out from one organism into the environment create many interactions that we are currently missing, it adds a layer of complexity.”

A Toxic Concept

In the early 2000s, Zimmer had his first inkling about keystone molecules while studying tetrodotoxin. The poison, made by adult California newts, among a variety of other creatures, was known to deter predators. His lab’s research showed that the chemical has an additional effect: It signals “danger” to larval newts, who then seek shelter from cannibalistic adults. The finding made him wonder whether tetrodotoxin was unique in its multifunctionality, or if other molecules play similarly pivotal roles in ecosystems.

With his graduate student Ryan Ferrer, now a chemical ecologist at Seattle Pacific University, Zimmer gathered more examples of multifunctional signals, and in 2007 they formally introduced the keystone molecules concept in a review paper in The Biological Bulletin. A keystone molecule, they wrote, is introduced into a community by one or very few species, usually as a defense mechanism or communication signal. It then takes on other meanings — mating, safety, danger, food — for other community members. The shrapnel of metabolic processes and species interactions generates a cascade of impacts.

“When we dive into the chemistry, we identify the intricate and sometimes delicate connections between members of the ecosystem,” Ferrer said. “It forms these connections that are easy to miss.”

In a 2013 paper, they identified four outstanding examples: tetrodotoxin, a neurotoxin produced by many animals including the newts, pufferfish and octopuses; saxitoxin, which is made by algae and makes shellfish toxic to predators; pyrrolizidine alkaloids, a widespread plant-produced poison that deters herbivores and attracts insects; and dimethylsulfoniopropionate (DMSP), a sulfur-rich compound produced by marine algae.

Across many ecosystems, these chemicals have widespread effects. DMSP, for example, is the ocean’s dinner bell: When the algae are eaten by krill and fish, the chemical leaches into the water and can form gas plumes over the ocean. Seabirds smell the plume from miles away. They follow it to feast on fish and then fly back to their nests, where they deposit excrement laden with nutrients that fuel plant growth on land.

“The molecules are transferred from trophic level to trophic level,” Zimmer said. “You end up with a broad number of interactions across a community, different species within a community, mediated by a single compound.”

Still, he lacked definitive proof that the molecules themselves were structural to ecosystems, affecting organisms beyond the ones that created them. No one had ever deliberately manipulated an ecosystem to test for “off-target” effects of the chemistry alone — until a slug scientist entered the picture.

A Mighty Smell

Patrick Krug can count on one hand the number of researchers who have ever studied wetland sea slugs from the genus Alderia. These gastropods, the size of a Tic Tac, are wildly abundant on the mudflats of San Francisco Bay, and pungent too. They smell “like a bad lemon,” Krug said. “It’s so gross. If I’m not sure if I’ve picked one up on a spatula, I sniff it.”

Before he got into sea slugs Krug was a postdoc in Zimmer’s lab. He helped measure tetrodotoxin for the newt studies and then set out on his own, starting a lab at Cal State to study the ecology and evolution of the Sacoglossa, a clade of more than 300 species of sea slug. Over the years he published half a dozen papers on the Alderia lifecycle. The more time he spent with them, the more curious he became about what produced their stink.

To find out, Krug enlisted the help of his graduate school roommate Eric Schmidt, now a biological chemist at the University of Utah, who has developed methods to manipulate the genes of chemical-producing animals. Previously, they had worked together to classify polyketide molecules from other sacoglossan slugs. Polyketides are produced by many organisms — bacteria, fungi, plants and animals — for color, sun protection, antibiotic effects, sex signaling or toxic defense.

Schmidt’s postdoc Paul Scesa isolated five polyketides from the Alderia slugs’ tissues and, with help from the biochemist Carole Bewley at the National Institutes of Health, characterized their molecular structures. They had never been described before. The team named the molecules “alderenes” after the slugs’ genus — and wondered about their ecological effects.

In the lab, Krug ran alderene taste tests with critters collected from the slug’s ecosystem. When presented with slugs, alive or dead, fish and worms rejected the meal outright. Crabs rubbed their faces against rocks to get rid of the taste. “It was like watching a teenager eat a hot chili pepper for the first time,” he said.