Does resistance really carry a fitness cost?

Abstract

Insecticide resistance mutations are widely assumed to carry fitness costs. However studies to measure such costs are rarely performed on genetically related strains and are often only done in the laboratory. Theory also suggests that once evolved the cost of resistance can be offset by the evolution of fitness modifiers. But for insecticide resistance only one such example is well documented. Here we critically examine the literature on fitness costs in the absence of pesticide and ask if our knowledge of molecular biology has helped us predict the costs associated with different resistance mechanisms. We find that resistance alleles can arise from pre-existing polymorphisms and resistance associated variation can also be maintained by sexual antagonism. We describe novel mechanisms whereby both resistant and susceptible alleles can be maintained in permanent heterozygosis and discuss the likely consequences for fitness both in the presence and absence of pesticide. Taken together these findings suggest that we cannot assume that resistance always appears de novo and that our assumptions about the associated fitness costs need to be informed by a deeper understanding of the underlying molecular biology.

Figure 1

Mechanisms of overcoming fitness costs associated with insecticide resistance. (a) Differential methylation of amplified copies of esterase-4 (E4) in the aphid Myzus persicae. Gene amplification of E4 in highly resistant R₃ clones (only five tandemly duplicated copies are shown here for simplicity) results in an increase in both the E4 transcript and E4 protein which can sequester and hydrolyse a range of organophosphorus and carbamate insecticides. However in the absence of insecticide, ‘revertant’ clones exhibit loss of both E4 expression and insecticide resistance. This loss of E4 expression is associated with loss of CpG sites within the amplified genes, resulting in gene silencing via demethylation. (b) Diazinon resistance evolution in the Rop-1 locus encoding esterase-3 on chromosome IV of the Australian sheep blowfly Lucilia cuprina is followed by evolution of a fitness modifier Scalloped wings (Scl) on chromosome III. This fits the classical model for the evolution of a fitness modifier (see text for discussion). (c) Gene duplication leads to a compound heterozygote in which both a susceptible (ace-1^S) and a resistant (ace-1^R) copy of the ace-1 gene are then found on the same chromosome. In this configuration any fitness costs associated with the ace-1^R allele will be offset by the permanent presence of the susceptible allele along side it in permanent heterozygosis.

Figure 2

Backcrossing a resistance gene (R) into a susceptible (S) genetic background is a pre-requisite for proper fitness comparisons. However, several generations of backcrossing (BC) are necessary to completely replace the ‘resistant’ genome with the ‘susceptible’ one and generate near isogenic lines (NIL). Whilst easy to do in the fruit flies, the difficulty of backcrossing strains of pest insects has hampered our ability to properly compare fitness costs (see text for full discussion).