Evolutionary Resistance
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 a French-led international team at the Universitéé
Montpellier II, 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. However, not all mosquito species exposed to high levels of carbamates and OPs
develop resistance. 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. The researchers determined that the G119S version of the
Aedes 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 Aedes aegypti populations.
Looking more closely at the Aedes 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 Anopheles gambiae, it only takes one base mutation to alter the code in the right
way; in Aedes 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 Aedes 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. (AAAS Press Release, 7/26/04).