Mate or hibernate? That's the question worm pheromones answer

July 23, 2008

GAINESVILLE, Fla. — If worms could talk, they might tell potential suitors, “I like the way you wriggle,” complete with that telltale come slither look. But worms send their valentines via signals known as pheromones, a complex chemical code researchers are now cracking, according to a study published today (July 23) in the journal Nature.

Scientists from the University of Florida, Cornell University, the California Institute of Technology and the U.S. Department of Agriculture have discovered the first mating pheromone in one of science’s most well-studied research subjects, the tiny worm Caenorhabditis elegans. But perhaps even more interesting is what the newly discovered pheromone also directs worms to do — hibernate.

At lower levels, the pheromone signals the male C. elegans to mate with its partner. But when the worm population grows and the food supply dwindles, the chemical signal increases and the cue changes from mate to hibernate. This discovery could help researchers find ways to combat more harmful worms that destroy crops and provide clues for scientists studying similar parasite worms, said Arthur Edison, a UF associate professor of biochemistry and molecular biology in the College of Medicine and one of the study’s senior authors.

“Even though it’s the same compound, it affects different behaviors,” said Fatma Kaplan, a postdoctoral associate in Edison’s lab and one of the study’s lead authors. “It’s two different life traits converging.”

In 2002, Cal Tech researcher Paul Sternberg discovered that male C. elegans were attracted to a signal the opposite sex was sending out, but scientists weren’t sure exactly what it was.

“C. elegans is one of the best-studied organisms on earth,” Edison said. “The entire cell lineage of the animal is known from fertilized egg to adult animal. Every single cell division had been mapped out. But until now, its small-molecule signaling has been poorly understood. We wanted to understand how C. elegans talk to each other, basically.”

About four out of every five animals on the planet is the same type of organism as C. elegans — a nematode, said Edison. Although the C. elegans worm, which is about 1 millimeter in length, is harmless to humans, many nematodes destroy crops or act as parasites in humans and animals, such as the large human intestinal parasite Ascaris lumbricoides. Because it is easy to grow and manipulate in the laboratory, C. elegans is a model for understanding the basic biology of humans, animals and other worms that threaten human health.

C. elegans worms are either male or hermaphrodite — meaning they feature both male and female reproductive organs — and to pinpoint how they communicate, UF researchers and their collaborators isolated the chemicals the hermaphrodites secrete and tested them on male worms.

Initial tests proved the males were attracted to the secretions when the hermaphrodites were fertile. Using mass spectroscopy and nuclear magnetic resonance spectroscopy — including a UF- and National High Magnetic Field Laboratory-developed NMR probe that allows researchers to test extremely small amounts — researchers isolated the three chemicals in these secretions that are responsible for the mating signal.

When tested individually, the chemicals produced little to no response. But the chemicals strongly attracted male worms when they worked in synergy with each other, said Edison, who also serves as director of the McKnight Brain Institute’s Advanced Magnetic Resonance Imaging and Spectroscopy facility and co-principal investigator of the National High Magnetic Field Laboratory.

But it was a chance collaboration with Cornell researcher Frank Schroeder that led to the paper’s biggest finding, Edison said. Schroeder had recently discovered what’s known as a dauer pheromone. These chemicals signal worms to enter a hibernation phase when the food supply is low. Schroeder’s hibernation pheromone and the UF-discovered mating pheromone were almost identical. Tests in worms revealed that mating pheromones also act as a dauer pheromones at high concentrations.

“It’s like a bell-shaped curve,” Edison said. “If (the pheromone level is) too low, it doesn’t work. If you add more, you get a nice mating response. If it gets high, the mating response stops and they go into hibernation mode.

“It makes nice ecological sense that (one compound) could be doing both jobs,” he added.

“But before this work, nobody in the whole history of C. elegans research had associated dauer formation with mating. Now these small molecules link the two behaviors.”

Researchers have been trying to find C. elegans mating pheromones for a long time, said Piali Sengupta, a professor of biology at Brandeis University, who agreed that it makes sense that the mating pheromone has a dual role in causing hibernation.

“This opens up the field,” Sengupta said. “This is just the beginning. There is going to be a lot more (research) coming out related to this.”

Edison and Kaplan’s collaborators include: Sternberg, Schroeder, Cal Tech researcher Jagan Srinivasan, UF researchers Ramadan Ajredini and Cherian Zachariah, Cornell researcher Rabia U. Malik and USDA researchers Hans Alborn and Peter Teal.

The research was funded by the Human Frontiers Science Program, the National Institutes of Health and the Howard Hughes Medical Institute.