The female fruit fly is a faithful lover, at least for a little while. As soon as she mates, she rejects all suitors for several days and spends her time laying eggs. Biologists have now found the switch that controls this coy female behavior, to the pleasure of male flies and disease researchers alike.
The basis for the female fly's temporary monogamy is a mood-killing protein called sex peptide (SP). Male flies inject SP along with their semen to guard against potential competitors and to induce egg-laying, but the peptide's target has evaded researchers for decades.
To track down SP's molecular dance partner, a team led by Barry Dickson, a biologist at the Research Institute of Molecular Pathology (IMP) in Vienna, Austria, introduced 13,000 virgin female flies to 13,000 eager males. In each female fly, a different gene had been turned off using a technique known as RNA interference. After every mating, the researchers counted the number of eggs that the females produced in 48 hours. Then they matched each female with another randy male. "If we managed to turn off the receptor for SP in a female," says IMP graduate student Nilay Yapici, "then she should lay few or no eggs and be as receptive as a virgin when she meets another male."
Of the 13,000 female flies tested, one fit the bill. Glowing antibodies were used to home in on the location of the target gene, which Dickson calls the SP receptor (SPR). It lit up in the female's sperm-storing organ and nervous system. Specifically, SPR clustered in neurons known to be involved in sexual behaviors. (SPR also showed up in males' nervous systems, although it is unclear what it does there.) Blocking the production of SPR in just those brain cells made females behave like virgins, even if they were anything but, the team reports this week in Nature. If a drug can be found that blocks SPR in mosquitoes, the researchers say, it could help combat malaria: Mosquito populations might crash as ever-frisky females mate instead of laying eggs.
"This is a major breakthrough," says Eric Kubli, a biologist at the University of Zurich in Switzerland. Whether mosquitoes use the same sexual behavior switches as fruit flies isn't certain, says Kubli. But a gene very similar in sequence to SPR is known in mosquitoes, he says, so the next step will be to knock it out.