Sexual attraction: finding the right switch

Developmental switches — genes that are necessary and sufficient to specify a particular anatomical part, such as the eye — have more or less become household concepts. This logic has now been extended beyond morphological development by the finding that a complicated behaviour is also determined by a switch-like mechanism, one that involves the alternative splicing of a single gene.

In fruit flies, courtship is mostly a male affair: the male's elaborate ritual is rather complex, and therefore would intuitively call for a complex genetic explanation. However, one of the many genes involved in the courtship ritual would indicate otherwise: strong loss-of-function mutations of fruitless (fru), which encodes a zinc-finger protein, specifically abolish male courtship, and weaker ones disrupt individual steps of the process. fru is therefore involved exclusively in male courtship and sexual orientation, and does not influence sexual morphology. Could fru be the switch gene for this particular set of sexual behaviours? This was first hinted at by the fact that males and females have differently spliced isoforms of the fru mRNA, but the idea remained to be tested.

The authors engineered lines of fly that contained male-only (fru^M) or female-only (fru^F) isoforms, and looked at the morphological and behavioural consequences. Consistent with the hypothesis that the male-specific fru isoform is required for male courtship, males that contain fru^F do not court. By contrast, females that contain either of the two fru^M isoforms behave like males: they court females (or males that make female pheromones) and do so by carrying out all but the last steps of the male courting ritual. The neat sex role-reversal induced by a single-gene isoform shows that the male-specific splicing of fru is necessary and sufficient for sexual orientation and behaviour.

How the sex-specific isoforms induce radically different behaviours is not clear: the authors of a second paper identify a functional circuit of fru^M-expressing neurons; however, the circuits are anatomically similar in males and females, so sex-specific differences must lie in how the circuit functions.

Several complex behaviours have been analysed genetically (see the Review on p521) and are indeed turning out to be quite complicated. However, the courtship example highlights the potential of opening up other innate, sex-specific behaviours to genetic scrutiny.