A California researcher recently discovered that worms from a particular strain of Caenorhabditis elegans don't like to eat alone. When placed near food, they scurry around looking for company. Worms from another strain, however, clearly prefer solitude. She and her colleagues then identified a small genetic mutation that determines this difference.

Another scientist, also in California, noticed that some male roundworms are distinctly deviant in their approach to females. He located a genetic anomaly that accounts for this strange behavior.

You might wonder whether any of this really matters. Should we care about a worm's social life?

Well, yes. After all, we may have similar genes, and even though mutations in these human genes would not be expected to produce the same kind of social isolation or sexual incompetence as in worms, the genetic pathways involved are likely to exist in humans, too. So what we learn from the worm genes may apply to various human disorders.

The solitary worms come from a strain of C. elegans called N2, whose progenitors were lifted out of a compost heap in Bristol, England, many years ago.

"Just as almost everyone who works in worms can trace his or her lineage back to Sydney Brenner, who started studying them in Cambridge, England," explains Cornelia Bargmann, an HHMI investigator at the University of California, San Francisco, "most experiments on worms are done with the strain of C. elegans that Brenner originally started studying—N2.

"These N2 worms are antisocial," Bargmann says. Put them on the kind of food they like best—a patch of bacteria—on the surface of a petri plate, and they will slowly disperse until they have a part of the patch entirely to themselves. Then they stay there alone and munch away. The same is true of about a third of all "wild" strains of C. elegans.

By contrast, worms from other wild strains are eager for company. As soon as they sense food, they swarm or clump together, forming eating clubs in certain areas of the bacterial patch (usually around the borders) while leaving the rest of the patch empty. Certain mutant N2 worms also behave in this way. "The original observations about this difference had been kicking around in newsletters and in lore for about 20 years," says Bargmann. A few years ago, she and Mario de Bono, a postdoctoral fellow in her lab, decided the difference was worth investigating. "We became interested in it because we were studying sensory behaviors," Bargmann explains, "and clearly these worms were sensing something about one another, possibly through pheromones."

Behavior is notoriously difficult to pin down, however. "As long as several different wild strains of worms were involved, you couldn't tell whether a particular form of behavior depended on many genes or on a single gene," says Bargmann. "Another difficulty was that the difference between these strains was seen in the behavior of populations of worms—not in individuals. You couldn't really score any individual worm for what strain it belonged to; you had to have a whole plateful of worms—at least 50 worms—to get a sense of what the effect was. It's hard enough to score behavior without having to score 50 worms." Besides, the researchers could never be sure whether a particular behavior resulted from the worms' own traits or whether it was influenced by the behavior of other worms, Bargmann explains. "It's really messy," she says.

Clean experiments became possible when de Bono discovered something that could be measured accurately in a single worm and served as a sign that the worm would search for lunchmates: hyperactivity.

The sociable worms were hyperactive—they kept moving around the food plate rapidly, not slowing down until they found eating companions, he observed. By contrast, the solitary worms moved very slowly all the time, grazing on food right from the start.

When the researchers set about looking for genetic differences between the hyperactive and slow-moving worms, they found a difference in just a few base pairs of DNA that correlated with hyperactivity in all strains of worms. This DNA difference produced a change in a single amino acid. "All the solitary worms—five different strains from Europe and America—have a valine at a particular position in the protein produced by the npr-1 gene, whereas all the social worms have a phenylanine at the same position," says Bargmann.

— Maya Pines

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"These worms like to eat alone," says Cornelia Bargmann, holding up a magnified picture of live but antisocial worms (left). Worms from a different genetic strain keep moving around the bacteria-covered petri plate until they find dinner companions and then clump together for meals (right).

Photo: Kay Chernush

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