Wait for it...Wait for it...It's Teh Gay Gene!

So does anyone want to lay odds on how long it will be before "discovery of the gay gene" gets spread like a crazed rhinovirus through the popular media? A recent press release announces the discovery that male fruit flies (Drosophila melanogaster) with mutations in the GB (genderblind) allele not only mate with female flies but also were attracted to - and try to mate with - male flies.

The mutation apparently alters perception of chemosensory cues. Two of the major chemical attractants in the world of fruit fly sex are 7-tricosene and cis-vaccenyl acetate: the flies taste the former and smell the latter. Flies unable to produce either or both of these chemicals are courted by males. Male flies who can't sense these attractants court other males and attempt to copulate with them.

Yael Grosjean et al. (1) report that this homosexual - or more accurately bisexual - behavior in fruit flies is controlled by glutamatergic synapse strength, i.e., ambient levels of glutamate in the nervous system. Glutamate is what's known as an "excitatory amino acid." It plays an important role as a neurotransmitter in the brain. Glutamate levels in the fly's nervous system are regulated at least in part by an amino-acid transport protein in the glia, the non-excitatory cells that feed and care for neurons. That transport protein is encoded by the genderblind allele.

The researchers could turn homosexual behavior on and off by genetic alteration of the abundance of genderblind genes or by pharmacological manipulation of the glutamate levels. Increased glutamate resulted in bisexual behaviors in the male flies since they attempted to mate with both males and females. They expanded their sexual repertoire.

The researchers propose a model for effect of glutamate levels on the flies' sexual behavior and compare it to a mammalian model proposed by Tali Kimchi et al. (2) Female mice that are homozygous negative (both copies of the gene are defective) for the Tprc2 gene (Tprc2-/-) display male courtship and sexual behaviors.

The Tprc2 gene encodes for the transient receptor potential (ion) channel 2; this is a ligand-activated ion channel. In the case of Tprc2, a biomolecule called diacylglycerol (DAG) is the ligand; DAG binds to the receptor which then opens and allows calcium ions to permeate the cell. As "transient" implies, the channels sense and respond to changes in the environment. The Tprc2 receptor is localized in the neurons of the vomeronasal organ (VNO) of mice. Both the major olfactory epithelium (layer of skin cells within the nose) and the VNO interact with pheromones that contol mating, aggression and gender identification. Kimchi et al. posit that VNO-mediated pheromones act in wild type Tprc2 females to suppress male behaviors and activate female behaviors.

Shah and Breedlove (3) opine that these results indicate that the preference to "mate as a male or female" is not irreversibly set during development. Well, at least in mice with their vomeronasal organs. This Nature "News and Views" snippet coyly states at the end: "Whether such simple rules dictate affairs of the human heart remains to be seen." Cue violins and cheesy romance novel artwork.

Sexual behaviors, and variations thereof, for both fruit flies and mice are strongly influenced by pheromones which in turn trigger specific proteins in the nervous system. However, the mechanisms are quite different: one relies on glutamate levels as influenced by a transport protein and the other by a relatively non-specific calcium permeable ion channel. Kinda complex, isn't it? Suffice it to say that transport proteins and ion channels are different beasts.

I will not be at all surprised to stumble upon a newspaper article or a benighted blog or message board that yammers incoherently "Genderblind is a 'gay gene.'" The next step from there is to extrapolate this to human sexual behavior; such an extrapolation is fraught with peril. Glutamate levels vary temporally and spatially in the mammalian brain. Changes in ambient glutamate affects mood and behavior and may not be readily analogous to Drosophila.

The spectrum of human sexual behavior is varied, more so than a fruit fly, thanks to our intricate brains. We are also not sexual slaves to our noses. Pheromones are not the major mating drivers in Homo sapiens that they are with the aforementioned bugs and rodents. Although homosexuality undoubtedly is biologically based, in humans this is highly likely to be due to multiple alleles, epigenetics and their interplay with environment. But will that stop folks from oversimplifying or worse - deliberately mis-using the information? Of course not! Well, OK, that's what I predict.

Science Daily offers these intro lines to an otherwise fairly accessible article about Grosjean et al.'s work:

While the biological basis for homosexuality remains a mystery, a team of neurobiologists reports they may have closed in on an answer -- by a nose.

But at the conclusion of the Science Daily article, the potential for this discovery may be more important for creation of genetically modified fruit flies that with agriculturally desirable behaviors:

Featherstone says it may someday be possible to domesticate insects such as fruit flies and manipulate their sense of smell to turn them into useful pollinators rather than costly pests.

There's something disingenuous about this. "Wow! Zow! Boffo Headlines! Scientists Closing in on Biological Basis for Teh Gay!" But then one reads the article, and finds the whisper at the end: "Non-Pesty and Useful flies can be bred based on our discovery." The latter isn't so - uh - sexy.

I must admit, I did like this description of a male fruit fly's courtship from the Grosjean article:

In the fruit fly...courtship typically begins when a male fly identifies and approaches a suspected conspecific female. To confirm his suspicions and to test whether she is sexually receptive, he will tap her with his foreleg (to evaluate nonvolatile pheromones via chemoreceptors on his leg), sing a species-specific courtship song (by extending and vibrating a wing) and lick her genitals (to sample pheromones).

Whoa! I'm swooning!

(1) Grosjean, Y., Grillet, M., Augustin, H., Ferveur, J-F., and Featherstone, D.E. (2007) "A glial amino-acid transporter controls synapse strength and homosexual courtship in Drosophila." Nature Neuroscience Advance Online Publication, Dec. 9, 2007.

(2)Kimchi, T., Jennings, X., and Dulac, C. (2007) "A functional circuit underlying male sexual behaviour in the female mouse brain." Nature 448: 1009-1014.

(3) Shah, N.M. and Breedlove, S.M. (2007) "Females can also be from Mars." Nature 448: 999-1000.