My background in population genetics holds that there are four main factors that affect the evolution of drug resistance:
- The initial frequency of resistance alleles.
- A higher frequency can greatly speed up the development of resistance.
- The number of different genes that affect the expression of resistance.
- In simple terms, if only one gene controls resistance then selection is relatively straightforward. If there are many genes it may take longer to assemble the right configuration of all the genes.
- The selection pressure exerted by drug application.
- If no drug is used there is no selection pressure. Similarly, if all individuals are killed there is no selection pressure since there are no survivors. Somewhere in between, the resistance alleles will have a selective advantage over susceptibility alleles.
- The relative dominance of resistance over susceptibility alleles.
- If a resistance allele is rare then it is found most often in heterozygotes. This becomes critical when one of the alleles is masked by the presence of the other. If resistance is recessive then heterozygotes appear susceptible and the rise of patent resistance can be significantly delayed.
Surveying allele frequencies in susceptible and derived resistant strains of parasite has shown that the frequency of resistance alleles can be as high as 25% (Beech et al, 1994). The number of genes that affect a trait can be affected by the method used to measure their effect. Allele frequency changes have been used to show a link between four different genes and ivermectin resistance (Blackhall et al, 1998a,b; Blackhall, 1999). I am currently focusing on the selection pressure exerted by the drug and relative dominance of different alleles involved in ivermectin resistance.
