Tuesday, December 25, 2007

Genderblind Flies

Here is our first submission by a PhD candidate studying genetics. She has chosen to remain anonymous for professional reasons. Anyone who wants to submit an article to me is more than welcome to do this. Enjoy!

Mate selection is a complex process in humans, as well as in Drosophila melanogaster, the fruit fly. In order to successfully reproduce, it is vital that one sex be able to identify a receptive member of the other. For flies, courtship rituals allow males to make this determination. This courtship involves physical contact that enables the courting male to assess his intended for repellant pheromone signals (those carried by other males and females that have already been mated), as well as a species-specific song created by wing vibrations, and additional pheromone sampling by oral-genital contact. In other words: a few rounds of fly foreplay. If the fly receiving these advances is successfully seduced, copulation may be attempted.

The Featherstone lab recently published a paper describing an increase in homosexual behavior by male flies. These flies had mutations in a gene they named genderblind. These mutant flies aren’t strictly homosexual. Whereas wild-type flies would always chose to mate with a female fly instead of a male fly when given equal choice between the two, the genderblind flies chose the male fly with the same frequency and intensity as the female fly. These results do not show that the flies preferred to mate with males flies – rather, it shows that the flies were unable to differentiate between male and female flies.

The genderblind mutation led to lower amounts of the genderblind protein being present in regions of the brain that are involved in pheromone sensing and response. They found that the amount of genderblind present inversely correlated with male-male mating attempts.

After a series of experiments, they concluded that the genderblind phenotype (the increase in homosexual behavior) was caused by an altered response to chemosensory stimuli. In particular, the mutant flies seemed unable to detect the normally inhibitory pheromones that male flies carry. They further showed that a drug which mimicked the effects of the genderblind mutation caused wild-type flies to exhibit a similar increase in male-male mating attempts. Restoring wild-type levels of genderblind in mutant flies returned their sexual behavior to that of wild-type. Both of these effects could be seen hours after the treatments, showing that it was the current brain chemistry that was causing the behavior, not a result of their developmental process.

It turned out that the increase in homosexual courtship was ultimately due to a reduction in the brain’s levels of extracellular glutamate. The normal excess of glutamate in the brain acts to desensitize the glutamate receptors, which in then reduces the glutamergic synapse strength. However, in genderblind flies, their reduction in extracellular glutamate led to an overall increase of the synapse strength of the glutamate receptors. This led to flies that overreacted to the chemical signaling in their brains.

Perhaps as a result to their overreaction to chemical stimuli, the flies attempted heterosexual as well as homosexual courtship at a higher frequency than wild-type flies. The genderblind flies also showed an increase in ectopic courtship – attempted copulation with nonsexual body parts, like heads. It may be that genderblind mutants are less sexually inhibited in general, not only in terms of homosexual behavior.

For flies as well as all forms of life, the reproductive drive is among the strongest impulses in nature. It could be that there are entire systems of suppression that have evolved to attempt to narrow the list of possible sexual partners to those which are most likely to produce offspring.

When I first heard about the paper the Featherstone lab had published, I was worried. I had feared that their results could lead to homosexuality being once again thought of as a disease or a lifestyle choice. After all, didn’t the paper show that drug treatment could curb it and return the flies to heterosexual behaviors? And clearly, the effects of the genderblind mutations were defects – they represented a behavior that is only found when something is wrong with the animal. I was waiting to begin hearing the religious right or similar groups start holding this research up as proof that no one is hardwired in their sexual orientation, that homosexuality is unnatural. That instead of being recognized as just another form of variety among the human species, it would be thought of as a treatable condition. With visions of an uncomfortable (if not worse) future, I felt more than just a little fear when I began to read the article.

Thankfully, after reading it, I felt relieved. The experiments they used were very straight-forward, and the results were stated as they were observed. They made no claims that their findings would apply to humans. One of the major reasons that flies are chosen as experimental models is their relative simplicity. Humans have significantly more complex genetics. We also have the undeniable influence of a very well-developed culture. Because of this, I do not believe that any sexual orientation issues will be able to be reduced to a single gene, or even a handful of genes. Our genes represent a starting point for what makes each one of us unique. They can give us predispositions and their own set of influences, but even those do not necessarily dictate the path of our lives.

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