Chumminess Of Roundworms Linked To Single Gene, Offering Insight Into Mechanisms Of Social Behaviors

The gene identified is closely related to the neuropeptide Y receptor gene in humans, which has previously been implicated in controlling appetite. This serendipitous finding offers the tantalizing suggestion, still in the realm of speculation, said the researchers, that some element of the roundworm gene has been conserved in higher species through evolution. Regardless, the finding would not suggest a genetic explanation for why some party goers nibble on their own and others cluster around the potato chips.

What it does offer, said the senior investigator of the study, Cornelia I. Bargmann, PhD, an assistant investigator of the Howard Hughes Medical Institute and a professor of anatomy at UCSF, is an avenue for exploring the relative contribution of single and multiple genes to the development of innate behaviors, particularly social behaviors.

In contrast to survival skills, like mating and feeding, social behaviors can develop in more than one successful manner amongst species and within species, and have evolved relatively often through time. Such so-called natural variations are dramatized in the big cats, tigers being solitary and lions social. They are also seen within humans, shyness being a courting strategy for some, and brazenness for others.

While it is the way in which environmental stimuli play the genetic cords of higher species that creates unique responses in complex animals, insights into the genetic component could offer some understanding of the way in which behaviors develop. Genetic influences are particularly pronounced in simpler creatures, which lack intricate character development.

The gene detected in the roundworm and humans could offer an avenue for exploring the way in which modifications in social behavior occur, said Bargmann. These genes produce receptors for neuropeptides, chemical messengers that modulate behaviors, such as anxiety, over an extended period, and it may be, she said, that variations in certain behaviors develop as these neuropeptide circuits respond in different ways to environmental stimuli over time. (Survival behaviors such as fighting or fleeing, by contrast, are regulated by neurotransmitters, which provoke immediate responses in the nervous system.)

"Neuropeptide pathways could be a widespread mechanism for generating natural variations in behavior, between species and within a species. Interventions that enhance or decrease neuropeptide function could have potent and long lasting effects on choices of behavior patterns," she said. "I'd be interested in seeing if it does represent a source of behavioral variation in other species."

Bargmann's more immediate focus, however, is on the discovery that roundworms' feeding behavior is dictated by a single gene, for it calls into question the prevailing assumption that innate behaviors result from numerous genes acting in concert, even in simpler species, such as fruit flies.

The researchers examined 17 species of roundworm, collected worldwide. All 12 social strains had one version of the gene and all 5 solitary strains another, and the variation hinged on a single amino acid change.

"The discovery that a clearly defined trait is accounted for by one gene--and by one nucleotide within that gene--was a shocker," said Bargmann. "It really is kind of remarkable."

All of the roundworms, more elegantly known as nematode C. elegans, displayed similar behaviors when food was limited or absent. But when they were placed on a lawn of bacteria, the solitary feeders plodded independently across their range, while their social brethren moved through their prey as a marauding herd.

Moreover, when the researchers genetically converted a solitary strain into a social strain, the animals exhibited all of the behavioral differences characteristic of the social strain. They gathered in groups, moved rapidly on E. coli and burrowed themselves into the cultured turf.

The two nematodes types often shared similar environments -- in one case two opposing strains were pulled from the same sod -- suggesting that both genetic variations thrive in the same environment under different conditions. "It appears that the behavior evolved once and spread throughout the nematode community on multiple continents," Bargmann said. "Of course, it is the way the roundworms respond to food, pheromones and other factors that ultimately prompts their behavior, social or solitary. And it is likely that the bacterial banquet revealed but a narrow view of a more complex behavior," said Bargmann. Still, the explanation for these responses lies in the variations in the two genes.

The questions Bargmann is pondering now, she said, are aligned with the size of her subject. "We want to put the social behavior we've observed in the larger context of our worms. What is it they recognize about one another? How is it they know they are with a member of their own species? Does the gene in solitary feeders discourage communal gathering by inhibiting sensory neurons that detect pheromones?"

But she's already thinking larger questions, too. "I've started watching mice," she said, "and watching schools of fish."

The UCSF study, co-authored by Mario de Bono, a postdoctoral fellow in Bargmann's lab, was funded by the Howard Hughes Medical Institute and The Wellcome Trust.