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In some cases, genetic resistance takes on a life of its own

August 09, 2005

For those concerned with the troublesome effects of genetic resistance to drugs and pesticides, the conventional wisdom of evolution offers a reassuring word: In the absence of the original chemical threat, most resistance mutations would cause a disadvantage to their hosts and might be expected to quickly leave the genetic landscape once the use of a drug or insecticide is suspended or withdrawn. But emerging research suggests that such assumptions need reconsideration. Working with the fruit fly Drosophila, researchers have obtained new evidence that in some cases, the mutations underlying resistance can actually offer an advantage to hosts, even in the absence of pesticide-and such advantages can lead to the resistance trait spreading widely in natural populations.

The work is reported in the August 9 issue of Current Biology by a group led by Richard ffrench-Constant at the University of Bath, United Kingdom.

Because the vast majority of mutations are deleterious-even mutations that offer an advantage in special circumstances-genetic alterations such as pesticide-resistance traits have often been thought of as evolutionary flashes in the pan. This assumption stems from the prediction that resistance mechanisms will always carry a so-called "fitness cost" that will work against a genetic trait over time. Like heavily armored knights transported from battlefield to city, resistant individuals would be expected to be at a disadvantage, genetically weighed down in the absence of the chemical challenge for which they are armed. This idea suggests that if we stop spraying one insecticide and start spraying another, resistance to the first should decline as a result of the decreased fitness conferred by the resistance trait.

Although this assumption is widespread, data to support this contention are not especially strong, according to the authors of the new study. Several technical factors confound the gathering of such data-for example, experimenters assessing fitness may only look at single traits, rather than making more-thorough assessments of fitness in the wild.

In their new work, the Bath researchers have shown that DDT resistance in fruit flies not only carries no fitness cost, but in fact confers an advantage when inherited through the female. This suggests that DDT-resistant female flies are passing on to their progeny some unknown advantage related to the genetic alteration that offers DDT resistance-in this case, the overexpression of a particular gene. The researchers looked at the effects of the DDT-resistance trait on fecundity and development at all life stages and went to great lengths to ensure that the DDT-resistant and -susceptible strains differed only by the resistance gene itself, thereby strengthening the evidence that the DDT resistance trait does in fact confer an advantage in the absence of DDT challenge.

These results hold important implications for the use of any drug, pesticide, or antibiotic because they suggest that genetic resistance will not always disappear when a pesticide or antibiotic is suspended or banned. These results also help explain why DDT resistance in fruit flies is in fact spreading globally, reaching a high frequency in fly populations long after DDT has been withdrawn.

Cell Press