Genetics and sexual orientation in fruit flies

So neuroscientists have made lesbian flies. Well, sort of. NYTimes story here, actual articles here and here (back-to-back articles in the prestigious journal Cell - you probably need a subscription to access the full text). Quick summary:

[One gene], the researchers are announcing today in the journal Cell, is apparently by itself enough to create patterns of sexual behavior - a kind of master sexual gene that normally exists in two distinct male and female variants.

In a series of experiments, the researchers found that females given the male variant of the gene acted exactly like males in courtship, madly pursuing other females. Males that were artificially given the female version of the gene became more passive and turned their sexual attention to other males.

As always, the NYTimes write-up makes a little bit too much of the study. In particular, it says that "The finding supports scientific evidence accumulating over the past decade that sexual orientation may be innately programmed into the brains of men and women." Um, these studies were done in fruit flies. It hardly seems that it should be necessary to point out that fruit flies have much simpler nervous systems than humans and are much less capable of complex behaviors and learning. I don't want to put up humans on a separate plane from animals - we are animals, still, and human sexual orientation does have an innate component - but it is really stretching the absurd to infer the genetics of sexual orientation in humans from fruit flies. (David Velleman makes a similar point.)

The significance of this study has nothing to do with whether homosexuality is innate in humans or not, but lies rather in the novel demonstration that a single gene switch can control a stereotyped behavior through the development of a neural circuit, in the same way that a single gene switch can control the development of body parts (the analogy is to the fly gene eyeless, which is necessary and sufficient for eye formation).

One of the funny things about the NYTimes article is that it depicts the scientists as shocked and disbelieving, e.g. "The observing scientist looked with disbelief at the show, for the suitor in this case was not a male, but a female that researchers had artificially endowed with a single male-type gene." In fact, this result is pretty well expected, and I imagine that the experimentor was looking on not with disbelief, but rather a sigh of relief that the experiment worked and the hypothesis was confirmed.

The "fruitless" hypothesis of male courtship in the fruit fly was proposed almost 10 years ago. See here (under "Biological Overview") for a nice, if technical, summary of how the gene fruitless was thought to control male courtship behavior. Basically, the gene fruitless can encode several different protein products depending on how the message is processed (alternative mRNA splicing), and males and females produce different protein products. These fruitless protein products are transcription factors that then go on to control the expression of other genes, ultimately leading to differences in neural circuitry and hence behavior. So this latest result is not that surprising in its essence - what's surprising is how clean the result was and how completely fruitless controls courtship behavior.

Even so, the results weren't quite as clean as the NYTimes made them out to be. Females expressing the male variant of fruitless carried out most of the male courtship ritual, but spent less time licking tthe court-ee than wild-type males did. They also spent less time courting than wild-type males did during the 8 minute assay (40% v. 90% - though this difference could be due to the fact that the assay ended when males succeeded in copulating, which was obviously impossible for the mutant females). But this is just details - overall, the result is really remarkably clean.

One final point: one interesting facet of the second study is that males and females don't have many obvious anatomical differences in the neural circuitry that is controlled by fruitless. I'll quote the article:

We do not think it is their gross anatomy. With the trivial exception of neurons innervating the reproductive organs, we detect only subtle differences in the numbers of these neurons and no differences at all in their morphologies or projections. Pending further studies at higher resolution, we tentatively conclude that sex differences in courtship behavior do not rest on differences in the production, survival, or connectivity of the neurons involved.

This conclusion offers a rather sobering perspective on the considerable effort that continues to be devoted to identifying and characterizing sexual dimorphisms in the mammalian brain. In Drosophila, the sexual behaviors of males and females are dramatically different and highly stereotyped; we can attribute this difference to a single splicing event in a single gene, and we can examine the neurons that express this gene at single-cell resolution. Yet even under these ideal circumstances, we still cannot find any anatomical differences that might account for the dramatically different sexual behaviors of males and females. This suggests that differences in neural chemistry, rather than gross neuroanatomy, might underlie the profound differences in behavior between males and females in Drosophila, and surely in many other species as well.

In a way, I'd have been disappointed if it was the gross neuroanatomy instead of subtle molecular and cellular differences. The fantastic complexity of the brain at every level of analysis from anatomy to molecules - even in the simple fly - is maddening at times, but it's what makes neuroscience such an interesting field to be in at the moment.