While several studies find homosexuality in humans and other animals is biological rather than learned, a question remains over whether it's a hard-wired phenomenon or one that can be altered.

A new study finds drugs or genetic manipulation can turn the homosexual behavior of fruit flies on and off within a matter of hours. While the genetic finding supports the thinking that homosexuality is hard-wired, the drug finding surprisingly suggests it's not that simple.

In fact, homosexuality in the fruit flies seems to be regulated by how they interpret the scent of another.

Dramatic result

Homosexuality is widespread in the animal world. But scientists have long debated whether, in humans a "gay gene" exists. Previous research in humans has suggested that how we interpret scents given off by another might impact our sexuality.

In the new work, University of Illinois at Chicago researcher David Featherstone and coworkers discovered a gene in fruit flies they call "genderblind," or GB. A mutation in GB turns flies bisexual.

GB transports the neurotransmitter glutamate to brain cells. Altering levels of glutamate change the strength of nerve cell junctions, called synapses, which play a key role in human and animal behavior.

Post-doctoral researcher Yael Grosjean found that all male fruit flies with a mutation in their GB gene courted other males.

"It was very dramatic," Featherstone said. "The GB mutant males treated other males exactly the same way normal male flies would treat a female. They even attempted copulation."

Overreaction

Other genes are known to alter sexual orientation, but most just control whether the brain develops as genetically male or female. It's not known why a male brain does male things and a female brain acts in female ways, Featherstone and his colleagues say.

"Based on our previous work, we reasoned that GB mutants might show homosexual behavior because their glutamatergic synapses were altered in some way," Featherstone said. "Homosexual courtship might be sort of an 'overreaction' to sexual stimuli."

To test this, the researchers genetically altered synapse strength, independent of GB. They also gave flies drugs to alter synapse strength. As predicted, they were able to turn fly homosexuality on and off, within hours.

"It was amazing. I never thought we'd be able to do that sort of thing, because sexual orientation is supposed to be hard-wired," Featherstone said. "This fundamentally changes how we think about this behavior."

Sense of smell

The team figured fly brains maintain two sensory circuits: one to trigger heterosexual behavior and one for homosexual. When GB suppresses glutamatergic synapses, the homosexual circuit is blocked, the thinking goes.

So they did more tests. As expected, without GB to suppress synapse strength, the flies no longer interpreted smells the same way. The smells in question come in the form of pheromones, chemicals that affect sexual behavior in much of the animal kingdom.

It is not known, however, to what extent human attraction is affected by pheromones. A study in 2005 found that when smelling a chemical from testosterone, portions of the human brains active in sexual activity were turned on in gay men and straight women, but not in straight men.

But at least among fruit flies, "pheromones are powerful sexual stimuli," Featherstone said. "As it turns out, the GB mutant flies were perceiving pheromones differently. Specifically, the GB mutant males were no longer recognizing male pheromones as a repulsive stimulus."

The research was published online today by the journal Nature Neuroscience.