1 The ester¹ allele

In the 1960s, the French government attempted to rid its Mediterranean coast of mosquitoes (Culex pipiens) in order to attract tourists. It did this by regularly spraying the mosquito breeding sites located along the coast (Figure 1) with organophosphate insecticides that kill the mosquitoes by inhibiting an enzyme called acetylcholinesterase in the nervous system. The treatment was successful initially but, by 1972, the mosquito populations had begun to recover (Raymond et al., 1998).

Figure 1  Map indicating the location where mosquitoes were sprayed (hatched area), consisting of a 20–25 km-wide belt along the Mediterranean coast.

Show description|Hide description

This figure comprises two maps; at the top, a simplified map of south-east Europe centred on France and at the bottom an expanded map of the French coastal region where mosquitoes were sprayed by the French Government in the 1960s. The treated area, indicated by hatched markings on the map, extended along a 20–25 km-wide belt along the Mediterranean coast, centred around Montpellier including Perols, Maurin and Montferrier.

Figure 1  Map indicating the location where mosquitoes were sprayed (hatched area), consisting of a 20–25 km-wide belt along the ...

To understand the reason for this recovery, the responses of different mosquito populations to exposure to the insecticide were examined. Researchers collected mosquito larvae from populations near the coast, where they had been sprayed with insecticide, and from populations north of the spray area, which had never been exposed to insecticide. They exposed both samples to the insecticide. In populations near the coast, which were sprayed regularly, mosquitoes were able to withstand and survive quite strong doses of the insecticide, but individuals taken from populations just north of the spraying area died when exposed to only weak doses.

Further research showed that the reason for the resistance in the coastal populations was a mutation at a locus called ester that encodes an esterase enzyme (called A1). The A1 esterase breaks down a wide range of toxins, including organophosphates. Mosquitoes that are vulnerable to the insecticide (and do not have the mutation) do not produce enough esterase to hydrolyse and thus inactivate the toxin. However, in resistant mosquitoes the mutated allele (called ester¹) alters the expression of ester by gene amplification (i.e. several copies of the same gene are found in the same genome). This causes increased production of the A1 esterase and, as a consequence, resistance to the toxin.

Scientists monitored the frequency of the ester¹ allele in populations at and near the coast for several years.

Maximise

Figure 2  Distance from the Mediterranean coast plotted against frequency of the ester¹ allele in mosquito populations in the south of France in the 1970s.

Show description|Hide description

This figure comprises three scatter graphs showing the distance from the Mediterranean coast plotted against frequency of the ester¹ allele in mosquito populations in the south of France for three dates in the 1970s. In each case the vertical axis is labelled frequency of the ester¹ allele and is marked from zero to 1.0 with intervals every 0.20. The horizontal axis is labelled distance from the coast/km and is marked from zero to 50 with intervals every 10 km. A curve is drawn through the numerous data points.

The graph on the left shows the data taken in 1973. At the coast, the frequency of the ester¹ allele is just above 0.6 which steadily declines to zero by 20 km from the coast (cluster of data points is tightly focused in the range 0.5−0.02, 5−15 km respectively).

The graph in the middle shows the data taken in 1975. At the coast, the frequency of theester¹allele is 1.0 which initially declines rapidly and then more steadily to 0.1 by ~35 km from the coast (cluster of data points is more scattered in the range ~1.0−0.0, 5−35 km, respectively).

The graph on the right shows the data taken in 1978. At the coast, the frequency of the ester¹allele is 0.95 which initially declines rapidly and then more steadily to 0.2 by ~35 km from the coast (cluster of data points is much more scattered range ~1.0−0.2, 5−35 km, respectively).

Figure 2  Distance from the Mediterranean coast plotted against frequency of the ester¹ allele in mosquito populations in the south of ...

In areas where mosquitoes were sprayed, ester¹ conferred a higher fitness on individuals carrying it, and these individuals passed the mutation on to their offspring. This resistance also spread to areas away from the coast (probably carried by mosquitoes migrating inland); however, as seen in Figure 2, it never reached a high frequency in inland populations. The reason for this is that the ester¹ mutation carries a fitness cost to mosquitoes carrying it. The overproduction of the A1 esterase has a side effect of interfering with cholinergic synapses of the central nervous system (those in which the neurotransmitter is acetylcholine). As a result, mosquitoes carrying the allele have a high susceptibility to predation and males have low reproductive success.

So why did the ester¹ allele increase in coastal populations despite it increasing the likelihood of predation and lowering reproductive success? The reason is that the selection coefficient of a particular allele depends on the net effect of that allele on an organism’s fitness. In the case of the mosquitoes, the fitness gains of resistance were greater than the losses due to predation (or other fitness deficits), but only in coastal regions where the mosquitoes were sprayed. Further inland, the ester¹ allele conferred no benefit because mosquitoes were not sprayed there. In these populations the ester¹ allele was disadvantageous because it raised the probability of predation and/or decreased reproductive success.