Insecticide resistance is an evolutionary problem at its core. Our challenge is to understand how mosquitoes that are resistant to insecticide spread and proliferate.
Evolution is the change in allele frequencies over time. Insecticide resistance evolves through adaptive evolution by natural selection. We will break this process down in two main components: mutations and selection (Figure 1).
Mutations are the fuel of evolution. Without mutations, there is no variation, and without variation, there can be no natural selection. Mutations occur, by and large, randomly in the genome as a result of errors in replication or repair. These mutations are most often harmful or at best neutral. But sometimes they have a beneficial effect, such as a mutation that confers resistance to insecticides for a mosquito. In any given population of mosquitoes there will be a range of susceptibilities to a given insecticide [FIG 1]. Such mutations could be single nucleotide changes in a specific gene, but they could also be larger changes such as gene duplications or deletions.
Mutations are extremely rare events, with estimates being as low as one in 100 million on any given location in the genome. You might wonder why resistance could be such a problem if mutations are so rare. Well, there are many mosquitoes in the population, and these mosquitoes have a relatively short generation time. Compare it to your chance of winning the lottery. If you just buy one ticket, that chance is extremely low. However, if you buy hundreds of thousands of tickets every month (about the generation time of a mosquito), your chances will go way up.
Natural selection results from a process whereby organisms which are better adapted to their environment tend to survive and produce more offspring. As a result, the next generation will contain more individuals descending from those better adapted parents [FIG 2]. Over generations you can observe a certain phenotype, and thus its associated alleles, increase in frequency in the population. To make this more concrete, let's imagine two mosquitoes: one that carries the resistance alleles and the other the wildtype, susceptible alleles. Both mosquitoes land on a mosquito net for their first blood meal. The resistant mosquito successfully feeds through the net and flies to the wall to digest the blood. The susceptible mosquito dies within minutes of touching the insecticide-treated bednet. The resistant mosquito lays her eggs a few days later leading to a hundred resistant offspring. The susceptible mosquito was never able to have any offspring. As you can see in this simple scenario, the frequency of resistance rapidly increased within one generation.
However, the story is not always this simple. First, resistance is not always perfect and mosquitoes carrying a resistance allele could still be impacted by the insecticide. Second, carrying a resistance allele doesn’t come without its cost. For instance, it has been shown that resistant mosquitoes could produce less offspring, have lower mating success, or less energetic reserves. These fitness costs could be the result of the mutations that impact the normal function of the gene or as a result of an upregulation of resistance associated enzymes, which are costly to overproduce. This is what we call a fitness trade-off: resistance is beneficial when insecticides are around, but it could lead to a lower fitness in the absence of insecticides. It is hypothesized that mosquitoes may evolve compensatory mutations that limit these fitness costs. We observe this in other organisms such as antibiotic resistant bacteria, however, such evidence in insects is scarce and whether this occurs for mosquitoes is still an outstanding question.
Taking all this together, whether insecticide resistance evolves depends on how big the fitness cost is and how many mosquitoes are exposed to insecticides. The more mosquitoes are exposed and the lower the fitness cost, the faster the spread of resistance.
