Yale Bulletin and Calendar

March 22-29, 1999

Volume 27, Number 25

Biologists unravel genetics
of fruit flies' sense of smell

A team of Yale biologists has identified 16 odor receptor genes in fruit flies -- the first found in any insect -- thus providing a promising avenue for controlling insects that carry deadly diseases and cause widespread crop damage.

Following the discovery of such receptor genes in mammals almost a decade ago, more than 25 research groups worldwide have attempted to find these elusive molecules in insects, according to John R. Carlson, associate professor of molecular, cellular and developmental biology and leader of the Yale team. He estimates that the fruit fly Drosophila melanogaster has more than 100 genes encoding odor receptors alone, which could be the biggest and most complex gene family in the fly.

"Our research demonstrates the enormous utility of the Berkeley Drosophila Genome Project, which already contains sequences for about 16 percent of the fruit fly's entire genetic code," says Carlson, whose team developed an innovative computer algorithm for searching the massive Berkeley data base. Carlson has already provided the newly discovered sequences to scientists requesting them for study of olfaction in moths, mosquitoes, honeybees and lobsters.

The search algorithm itself now is being sought by scientists working on completely different problems, Carlson says, because the algorithm can identify not only receptors but channels, transporters and other important membrane proteins needed for normal functions of a cell.

The algorithm was developed in collaboration with Yale biologist Junhyong Kim. Working with Yale postdoctoral fellows Peter J. Clyne and Coral G. Warr, Kim developed a computer program to hunt for proteins with "transmembrane domains," which Carlson believed would have the chemical makeup necessary for penetrating the cell membrane where receptors are embedded.

After identifying the first gene, the scientists went back to the computer to search for similar proteins, eventually ferreting out 15 more olfactory receptor genes, which are widely dispersed in the genome, and which all code for proteins with seven transmembrane domains.

"Remarkably little has been known about how an individual olfactory receptor cell chooses which receptor gene to express," says Carlson. "Recently, we discovered evidence that the Acj6 gene plays an important role in fruit flies in determining the odors to which a neuron will respond -- for example, whether a particular neuron responds to an apple or a banana."

Even though fruit flies and humans are separated by 800 million years of evolution, their genetic codes are remarkably similar, as demonstrated recently by Yale researchers who showed that a transplanted human gene can suppress the growth of cancerous tumors in fruit flies. Therefore, Carlson's discovery is expected to help neurobiologists map out brain wiring for the entire olfactory system not only in insects but in humans.

"We have many experimental options in Drosophila that are much easier than those in mammals," he says, adding that the insect's olfactory system is relatively simple, containing only on the order of a thousand receptor neurons. "For example, by selectively disabling or over-expressing these newly identified fruit fly genes, we can look for changes in odor sensitivity and behavior."

A long-term goal is to use this newfound knowledge to turn off olfactory neurons that insects use to locate potential mates, or the neurons that help them find the crops or humans on which they normally feast.

In the February issue of the journal Neuron, the Yale researchers also report that different odor receptor genes initiate expression at different times in development, with at least one of those genes expressed at a time when nerve cells in the antenna are still growing out toward their neuron targets in the brain. "This finding suggests that some of these receptors may be playing an important role in the development of the olfactory system, as they are believed to in vertebrates," says Carlson.

In Carlson's lab, computer searches of the Drosophila genome were augmented by behavioral studies, which helped the biologists identify the Acj6 gene. They screened for abnormalities in odor detection by observing which flies jumped when given a sudden whiff of an odor. Those with faulty Acj6 genes had a severe loss of sensitivity to a number of odors. Some neurons had lost sensitivity to all odors, and others became tuned to an entirely different set of odors. While they might fail to react to bananas, for example, they might react instead to strawberries.

The isolation of these genes in Drosophila should allow many new types of investigations of their function. Next, Carlson and his colleagues hope to confirm their observations by identifying which odors interact with individual receptors. "We haven't demonstrated directly that the products of our genes bind odorants, but I will be very surprised if they do not," Carlson says.

T H I SW E E K ' SS T O R I E S

Yale strengthens Faculty of Arts and Sciences
Nobel laureate to visit Yale as Chubb Fellow
Biologists unravel genetics of fruit flies' sense of smell
Yale announces moderate increase in term bill for the seventh straight year
Endowed Professorships: Margot E. Fassler and Rogers M. Smith
Exhibits, symposium look back at the Pop art of the Sixties
Area performers to lift voices in memory of noted conductor
Slifka Center celebrates new Media Arts Endowment with preview screening . . .
Lecture series will explore role of technology in today's culture
Noted Scottish sociologist will be featured speaker in campus events
Special program at ISM marks publication of Bryan Spinks' book . . .
Area artists invited to participate in second annual 'City-Wide Open Studios' . . .
Off-campus concerts
Conference will examine issues facing gays and lesbians in the workplace