Fruit Fly Pheromone Receptor First Ever Discovered Linked to Specific Sexual Behavior

For the first time in any animal, Duke University Medical Center researchers have linked a single pheromone receptor in the fruit fly to a specific sexual behavior.

Pheromones are chemical signals exuded by many animals — including humans — that serve as stimuli to evoke behavioral responses in other individuals of the same species. Pheromones often attract members of the opposite sex and provide important cues during courtship and mating.

Yet little is known about pheromone receptors, which are the protein switches nestled in cell membranes that trigger responses to pheromones, said Duke Medical Center geneticist Hubert Amrein, Ph.D., senior author of the study.

Now, he and co-author Steven Bray, also of Duke, report that male Drosophila fruit flies lacking one type of taste receptor have difficulty recognizing females. Although the males initiate the courtship ritual, the flies’ mating dance stalls when they apparently fail to detect the proper chemical cue from females. The sexually aberrant flies otherwise behaved normally, the researchers report in the Sept. 11, 2003, issue of Neuron.

“Scientists have been chasing pheromone receptors in animals for a long time with little success,” Amrein said, noting that although putative receptors have been found, tying those to specific behaviors had remained a major challenge. “Now, we have identified a receptor and a very specific aspect of courtship for which it is required.”

The work was funded by a grant from the National Institutes of Health.

Like mammals, insects display complex mating behaviors, many of which are triggered automatically in response to pheromones or other stimuli, Amrein said. Although the same principles likely underlie the behavior in all animals, he added, flies’ simpler nervous system makes them an ideal model for study.

Courtship in Drosophila includes a regular sequence of behaviors, which are critical for mating, Amrein explained. First, a male identifies a female visually. The male then approaches the female and touches her with his forelegs — which contain one of the flies’ taste organs — in a behavior known as tapping. After detecting pheromones from the female, the male produces a courtship song through rapid wing vibrations. The receptive female slows, allowing the male to investigate further with his labellum, the fly equivalent of a tongue. Finally, the male fly begins bending its abdomen as required for copulation, and the two mate.

In their search for pheromone receptor genes, the researchers explored the location of some 25 of 70 known taste receptors on the fly’s body. They found that one such candidate pheromone receptor, encoded by a gene called Gr68a, showed up only on the forelegs that males use in the tapping stage of courtship. Also, found the researchers, the activity of the Gr68a gene was governed by a gene that controls many aspects of sexual differentiation in flies.

The researchers found that male flies lacking the neurons that express the Gr68a receptor spent less time courting females and, as a result, mated significantly less often than normal flies did. Those deficient flies that did mate successfully took twice as long to do so in comparison to intact males.

Also, found the researchers, males lacking the Gr68a-expressing neurons initiated courtship more often than normal but the ritual stalled after the tapping stage, when males apparently failed to receive the pheromone cue from females. Flies lacking only Gr68a showed the same dysfunction as those lacking the neurons completely, a result which links the behavior directly to the taste receptor, Amrein said.

“It’s quite remarkable that a single gene receptor, expressed in just a few cells of the entire male fly, plays such a crucial role in the courtship process,” Amrein said. “When you knock out the function of the gene, the flies show a serious mating deficit.”

Although an earlier study found that mice lacking 16 genes thought to include pheromone receptors exhibited abnormal sexual and aggressive behavior, this is the first study to clearly link a single pheromone receptor to a specific mating behavior, Amrein said.

Besides chemical sensing, courtship in flies involves visual and auditory cues. Therefore, Amrein said, the finding in fruit flies is a step toward understanding how the brain integrates different kinds of sensory input and translates those signals into complex behaviors critical to reproduction and survival.