Thursday, July 3, 2008
Bisexuality in Drosophila
The fruit fly, like many organisms, has a stereotypical courtship ritual that precedes mating. After noticing a female, a male fly will follow her with a persistence that is strangely reminiscent to me of behavior that can be observed in any local pub on a busy night. The male will then tap the female with his foreleg, which allows him to sense her pheromones through chemoreceptors on his leg, and verify whether she is sexually receptive. If so, he will extend one wing and vibrate it, producing a species-specific courtship song. He also licks her genitalia to further test her pheromones. Of course these last few steps aren’t as noticeable at the local bar, and if they are you may be in the wrong place (perhaps a strange fetish pub). If she doesn’t reject him, he mounts her and attempts to copulate.
See the ritual here:
A fruit fly’s ability to discriminate between males and females is based on visual, auditory, and chemical cues, such as the pheromones 7-tricosene and cis-vaccenyl acetate (cVA). Flies that don’t produce these pheromones are deemed female and courted by other males. Mutant flies that cannot sense the pheromones attempt to copulate indiscriminately with males and females. Normally, however, homosexual behavior in drosophila is relatively rare.
Earlier this year, a joint research team from France and America set out to determine what the biological difference between bisexual and heterosexual flies is. Is it that bisexual flies have difficulty sensing pheromones like 7-tricosone and cVA, or that they are sense the pheromones and are attracted to the opposite sex? What is the mechanism that causes that difference in attraction?
The group identified a mutation in drosophila that drastically increased homosexual encounters. They named it genderblind (gb) due to the resulting phenotype, which exhibited bisexual behavior. They determined, using an immunoblot, that the gb mutation causes a reduction in gb protein quantity. An immunoblot is also known as a western blot, and involves separating proteins with gel electrophoresis and then probing for specific proteins with antibodies that have been raised against them (presence of the protein will invoke an antibody response).
In order to determine if homosexual behavior in flies was simply a result of the misinterpretation of sensory cues, the group manipulated visual and chemosensory cues and measured fly response. They found that, although reducing the availability of visual cues affects the ability of the fly to discriminate between sexes, it was not enough of an effect to explain gb behavior. When they exposed the gb flies to mutant males that did not produce 7-tricosene and cVA, homosexual behavior was reduced to wild-type levels. When they applied these pheromones topically to the mutants, however, homosexual behavior from the gb flies was restored. This suggested that gb flies sense the pheromones, but interpret them differently than wild-type flies.
The group was able to identify the genderblind protein as a glial amino-acid transporter subunit and a regulator of glutamate in the central nervous system (CNS) of the fly. One function of glutamate is to reduce the strength of glutamatergic synapses through desensitization. The gb mutants had reduced genderblind protein levels and lower levels of extracellular glutamate. This resulted in increased glutamatergic synapse strength in the CNS. A glutamate antagonist administered to gb flies caused them to revert back to wild-type sexual behavior, indicating that the stimulation of glutamatergic circuits is responsible for the homosexual behavior. Additionally, inducing the overexpression of glutamate in the CNS of the fly caused an increase in homosexual behavior in both gb and wild-type flies.
Amazingly, the homosexual behavior could basically be turned on or off by manipulating glutamate transmission. The researchers suggest that this implies there is a physiological model for drosophila sexuality in which flies are pre-wired for both heterosexual and homosexual behavior. The homosexual behavior, however, is normally suppressed by genderblind proteins. A similar model has been proposed for mice.
So, the natural question is: what, if anything, does this say about homosexuality or bisexuality in humans? Well, the authors of the study state that genderblind has a high homology to a mammalian protein, the xCT protein. This is a cystine/glutamate transporter and may be an important regulator of glutamate in the CNS, similar to genderblind in the fly.
Despite this similarity, however, in my opinion it is improbable that a relationship between xCT protein levels and bisexuality/homosexuality that is similar to the one in drosophila and genderblind protein exists in humans. This isn’t to say there couldn’t be a correlation, just that the direct connection seen in fruit flies would appear too simple to be a basis for human sexual orientation, which is probably governed by a number of gene-protein relationships. So, while glutamate levels could play a part in suppressing homosexual behavior, they probably couldn’t act like a “bisexuality-switch” they way they do in the fruit fly.
Grosjean, Y., Grillet, M., Augustin, H., Ferveur, J., Featherstone, D.E. (2008). A glial amino-acid transporter controls synapse strength and courtship in Drosophila. Nature Neuroscience, 11(1), 54-61. DOI: 10.1038/nn2019