By Janelle Weaver

The indifference of some mosquitoes to a common insect repellent is due to an easily inherited genetic trait that can be rapidly evolved by later generations, a new study suggests.

By selective breeding, James Logan and colleagues at Rothamsted Research in Harpenden, UK, created strains of Aedes aegyptimosquitoes in which half of the females do not respond to DEET (N,N-diethyl-meta-toluamide) -- a powerful insect repellent. They suggest that this rapidly evolved insensitivity is due to a single dominant gene -- one that confers resistance even if the trait is inherited from only one parent.

The researchers have not identified the gene that they propose is responsible for DEET resistance, or precise details about its workings. They did, however, find a type of odour-sensing cell that responds to DEET in most mosquitoes but is less sensitive to the repellent in the resistant ones. Their findings are reported today in Proceedings of the National Academy of Sciences.

"That there might actually be a gene lurking in the background in mosquitoes that causes DEET resistance is the single most surprising result," says Leslie Vosshall, who was not involved with the study and who investigates the neural and genetic basis of odour perception in mosquitoes at the Rockefeller University in New York City. "This hasn't really been reported before."

Propagating pests

Aedes aegypti is a species of mosquito that causes yellow fever, dengue fever and other viral diseases. Its blood-sucking females are not all cowed by DEET: around 13% of the laboratory populations tested by Logan's team would land on human arms covered in the repellent.

Researchers had previously found weak evidence that DEET resistance could be inherited in these mosquitoes, says John Brookfield, a coauthor of the paper and a geneticist at the University of Nottingham. But after picking out the DEET-insensitive females, the team found that in a single generation of breeding with untested males, they could create a strain where 50% of the females did not respond to DEET. That proportion remained relatively stable across subsequent generations of selective breeding.

This fast pickup and later stability suggests that a single gene, rather than an aggregation of multiple genetic traits, is key for DEET detection, Brookfield says -- at least, in the population the researchers studied. And when the nonresistant mosquitoes were later mated with the resistant population, around half of their offspring were insensitive to DEET -- suggesting that the gene is dominant. A previous study on the fruitfly, Drosophila melanogaster, had found that a nondominant trait could lead to inherited DEET resistance.

Insensitive types

Trying to narrow down what the gene could be doing, the researchers focused on the odour-sensing cells found in antennae, which are known to detect DEET and other chemicals. Though some studies have suggested that DEET works by jamming neurons that sense human odours, others have picked out neurons which seem to specifically respond to DEET.

The team found that odour-sensing cells in general were less sensitive to DEET in resistant females compared with cells in nonresistant females. But they also spotted one type of neuron that showed distinctly lower responses to high DEET concentrations in the repellent-insensitive females. Any gene responsible for this effect might alter that cell so that it could not recognize DEET or it might mutate an odorant-binding protein that delivers DEET to a receptor, the team speculates.

Vosshall says that the study shows there is a genetic basis for sensing DEET but it doesn't resolve how the resistance works. "What remains to be shown is a causal link between the effects on the antenna and insensitivity to DEET," she says. The authors excluded from their analysis one set of neurons that were missing in insensitive mosquitoes, she points out, which could explain why they could not sense DEET.

Whatever the molecular mechanisms involved turn out to be, the study further affirms that repellents like DEET may lead to resistance over time if used to control mosquito-borne disease on a large scale, says Logan. He next wants to test the evolution of DEET sensitivity using wild populations of mosquitoes, including those that spread malaria. "We're not saying that repellents shouldn't be used," he says. "But we have to understand how they work before we can use them properly."