Gay love on the fly
May 7th, 2008 | Published in Neurobiology | View blog reactions
I will be back on Monday (I deserve a holiday once a year!), but in the meantime you can read this article written by yours truly, but edited and published by the Peak, Simon Fraser University’s independent newspaper. I must have been the only consistent science contributor in - say, three years or so? The editing is not always great when it comes to science articles, but they did quite well this time, apart from italicizing “wild-type”, “flies”, and introducing (or tolerating?) some awkward syntax here and there. The article is more of a reflection on the results of the recent study on fruitless flies, results I have already talked about on this blog, and it has been written for a general audience. Feedback and comments are welcome. Next up will be a review on Xubuntu 8.04 Hardy Heron, and of course, the second part of the “writing a blog disclaimer” series. Until then…stick around!
Gay love on the fly
by Giovanna Di Sauro
We have known about gay fly males for quite a while. In fact, the fruitless, or fru, mutants were initially created using X-ray radiation in 1963, and there is a 1989 paper describing the effects of the fruitless defects in males, tracking them back to a chromosomal inversion probably caused by DNA breaks and repairs following radiation exposure in the original strain. Although the BBC suggestively calls the results of a recent study conducted on these flies a “mind-control sex swap,” this is definitely not the case: one characteristic of fruitless flies is that their sexual characteristics are perfectly normal — the males are fertile and so are the females, and their bodies are not deformed. This new study completes a series of research aimed at identifying the genetic and neural components in a model of sex-linked innate behaviour — courtship in fruit flies — and has some implications for the way we think of the relationship between genes and behaviour.
What is the reason for studying fruitless flies? In Drosophila melanogaster, the common fruit fly, sexual orientation and courtship are very straightforward. The male is the only one that can be said to display courtship behaviour: when a male intends to court a female, it uses wing vibrations to produce a “courtship song.” This song can be identified because of the specific frequencies of the sounds emitted by the male. There are two “modes” of emission, known as the sine song, with a frequency of approximately 140–170 Hz, and the pulse song, constituted of brief and repetitive amplitude modulations in a range of approximately 150–300 Hz. Females respond by allowing the male to copulate (or not; whether the male is successful depends on a variety of other factors, including winning “fights” with other males).
It was already known that fruitless encodes a gene product necessary for the determination of sex-specific courtship behaviour in flies, and that the transcripts of this gene exist in two main versions produced by alternative splicing: a male version and a female version. A previous study done showed that the male version is necessary for the determination of male courtship behaviour and sexual orientation. The gene is, in fact, also able to induce male courtship behaviour in females when researchers artificially induce the male-specific expression. On the other hand, loss of male-specific fruitless in males causes the disappearance of all typical male courtship behaviour. This is further complicated by the fact that there are several different alleles (variants) of the fru gene, able to alter not only courtship, but sexual orientation as well. For example, males with certain mutant forms of fru display an enhanced form of homosexual behaviour — with males literally chasing each other and creating courtship “chains.”
In a study published this April in the journal Cell, researchers from Yale and Oxford University looked at the neuronal circuitry expressing the products of the fru gene in male and female flies, and investigated what happens when one activates this neuronal circuit in fru mutants of both sexes. The experiments showed that activating this circuit results in different responses in males and females, and that the responses are dictated by the version of the fru protein expressed by the animal. Thus, wild-type males and male-fru-expressing females can produce the wing movements and the courtship song, whereas wild-type females will move their wings and produce a sound, but not a courtship song. However, females will “sing out of tune,” because the ability to “sing in tune” is carried out by higher-order neurons that are probably not present or are inactivated in females.
Researchers have discovered methods of controlling neuronal activity, and thus manipulating fly courtship behaviour. Shining light on the neurons, which expressed a light-activated ion channel, artificially activated the neuronal circuitry. When positive ions are allowed into neurons by ion channels, the neurons depolarize and the depolarization wave, or action potential, moves all along the membrane of the neuron until it reaches the synapse, where it causes neurotransmitter release. All you need to do to activate a neuron in a controlled way is to make it express an ion channel that can be controlled.
How did researchers make sure that the channels were present in the neurons they are studying? They used a promoter specific to those neurons, so that the gene coding for the channels made protein only there. A promoter is a stretch of DNA that has a role in determining where the gene is expressed in the body — and what better promoter to study fru-expressing neurons than the fru promoter?
After the researchers had caused the right neuronal activity in the right places, using these methods, they observed the behaviour of single flies and couples. In a short video published by New Scientist about this study, the narrator says that “to make a female sing like a male, all you need to do is to turn on one gene, and chop her head off.” In fact, the head of female flies being observed was chopped off to facilitate the observations, as “singing” usually requires interaction with another fly, and it is intermittent — all of which is not helpful if you want to analyze the song of that one fly in the experiment. This also helped to separate the ventral ganglion from the head, increasing the success rate of the experiments, which would have otherwise been only around 1.7 per cent.
By now you might be wondering whether the fruitless gene is present in humans. While Wikipedia states that the fruitless gene is not present in mammals, an independent search shows that humans might have a homologue of the fly gene. The name of the homologue is ZBTB22, a gene predicted to be a transcription factor and a zinc finger DNA binding protein, just like fruitless is. Does this mean that it has the same function in humans? Well, given that we do not produce courtship songs using wings, and that sex determination is very different in humans and flies, it probably doesn’t.
Apart from the results and the media hype around fruitless flies, you might still be wondering what the scientific implications of the study are. What the results suggest is that behavioural differences between the sexes might not be necessarily due to differences in neural circuitry, but in the presence or absence of sex-specific regulators of such circuitry. This means that, although it is usually true that there are significant differences in the overall neuronal structure of males and females (with males sometimes having extra neurons dedicated to male-specific behaviour, the fact that some shared circuitry might also contribute to fundamental sex-specific behaviours is also something that needs to be considered.
But what are the more general philosophical implications of these studies on fruitless flies? Psychologists believe that our genes might be able to set a range of potential behaviours for each individual, and that interaction with the external environment determines where he or she sits in that range. According to behaviourism, a philosophy of psychology developed in the ‘60s, interaction with the environment (and possible conditioning that might be exerted by external conditions) is fundamental to the development of behaviour. One of the founders of behaviourism, John B. Watson, is known to have said that he could create, starting from any 12 infants, any behaviours and personalities he wanted, simply through conditioning and applying other behavioural techniques. While this extreme view is now generally discredited, it is still widely believed that, in general, genes alone are not able to completely determine behaviour, and therefore that no genotype is sufficient, on its own, to completely determine and elicit a given behaviour.
The results of the studies conducted on fruitless flies are a proof of principle that this is in fact possible in animals, and that at some certain behaviours can be completely determined by genetic makeup. There is a caveat to this statement: the gene needs to be necessary and sufficient to generate this behaviour, as is the case with fruitless and courtship behaviour in fruit flies. This does not imply that all behaviours in animals are strictly determined by their genetic makeup, but it does effectively prove that this can possibly happen, at least for some specific innate behaviours. Some might oppose that this does not extend to humans; after all, human behaviours are also affected by cultural norms, which means that humans might experience a higher pressure from their social environment to conform to certain behaviours.
However, we need to consider the fact that, at a cellular and molecular level, humans and flies are surprisingly similar. Studies on fruitless flies, from the ‘60s until now, have shown that a single gene, in this case a key behavioural regulator expressed in a sex-specific manner, can activate a neuronal circuit, and that such activation is sufficient and necessary to produce a specific behaviour, which is therefore already determined at a molecular and cellular level. This opens up the possibility that gene-specific regulation of neuronal pathways affecting or determining behaviour might be possible in other animals, and maybe even in higher organisms such as humans.
© 2008. The Peak Publications Society
Male fly image courtesy of Wikipedia Commons
Clyne, D., Miesenböck, G. (2008). Sex-Specific Control and Tuning of the Pattern Generator for Courtship Song in Drosophila.. Cell, 133(?), 354-363.
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