Researchers have identified that a specific point in the genetic code appears not only to control an organism's resistance to a class of pesticides but also to significantly influence the ability of an organism to evolve such resistance at all. Identifying such specific and strong constraints on short-term evolutionary change are likely to help ecologists and public-health experts understand, and potentially predict, the ability of particular species to quickly develop resistance to substances such as insecticides. The new work also illuminates the kind of genetic technicality that can shape evolution.
The work, performed by an international team led by Mylene Weill of the Université Montpellier II (France), concerned the ability of mosquito species to develop resistance to two major classes of insecticides, carbamates and organophosphates (OPs). Previous work had shown that a single base-pair alteration, G119S, within the mosquito's version of the AchE1 gene conferred high levels of resistance to these insecticides. Not all mosquito species exposed to high levels of carbamates and OPs develop resistance, however. For example, Anopheles gambiae, the mosquito vector for malaria, is able to develop resistance in this way, whereas Aedes aegytpi, the vector for yellow fever and dengue fever, has never developed high levels of resistance.
The new study reveals the reason for this striking discrepancy in adaptation. First, the researchers determined that the G119S version of the Ae. aegypti AchE1 protein was indeed resistant to insecticide action in the test tube, suggesting that the mutation would confer resistance to the mosquito in principle but that for some reason the mutation does not appear in Ae. aegypti populations. Looking more closely at the Ae. aegypti gene sequence for AchE1 revealed the answer. The researchers found that in this species, the three-letter DNA code at glycine position 119 is different from that found in the other mosquitoes studied thus far. The difference is "silent," that is, the gene still codes for the same amino acid at the 119 position. But it means - critically, as it turns out - that a single mutation of the site cannot result in the G119S change needed for resistance. In A. gambiae, it only takes one base mutation to alter the code in the right way; in Ae. aegypti, it takes two adjacent base mutations - a far less likely event.
The researchers went on to sequence the 119 position in 26 natural populations of Ae. aegypti in 12 countries and found that in all cases the three-letter codon at this position was the same, fitting with the lack of AchE1-based resistance in this species observed worldwide. They also showed that the "constrained" codon is present in 31 of 44 additional mosquito species, almost all of which indeed appear to have failed to develop resistance. Among those species with the codon version that easily mutates to confer resistance, about 50% have already developed high AchE1-based resistance. Most of the others are not insecticide-controlled.
Mylène Weill, Arnaud Berthomieu, Claire Berticat, Georges Lutfalla, Vincent Nègre, Nicole Pasteur, Alexandre Philips, Jean-Paul Leonetti, Philippe Fort and Michel Raymond: "Insecticide resistance: a silent base prediction"
Published in Current Biology, Volume 14, Number 14, 27 July 2004, pages R552-R553.
Materials provided by Cell Press. Note: Content may be edited for style and length.
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