Contents - Faperta

Molecular Techniques for Developing New Insecticide Molecules 497
Selective Sweeps and Genomic Consequences
One feature of the evolution of insecticide resistance in the fi eld is the rapid spread of resistance
alleles after the initial outbreak. Since it happens so quickly, there is little time for
recombination to separate the favored resistance gene from the particular combination
(haplo-type) of closely linked genes where it appeared fi rst. It is likely that the sweep of
mutant esterase/organophosphate hydrolase genes in organophosphate-resistant blowfl ies
(Newcomb et al., 1997; Campbell et al., 1998; Smyth et al., 2000) replaced most of the variation
throughout the cluster of ten esterase genes in which it lies with a couple of wholecluster
haplotypes. This cluster makes up a large proportion of the detoxifying esterase
genes in the blowfl y’s genome (Claudianos et al., 2002). Probably, similar sweeps have
occurred in clusters containing resistant mutants of P450s and GSTs (Russell et al., 1990).
A major reduction may have occurred in the genetic variation in this species’ chemical
defense system in a short span of time. There may also be additional detoxifi cation systems
beyond the three major gene families so far studied. In addition to direct fi tness costs in
the absence of insecticide that may occur for some resistance mutants, there may also be a
substantial “opportunity cost” in terms of lost variation with which the species can respond
(Batterham et al., 1996).
Conclusions
There is a continued need for identifying new insecticides either to be used alone or in
combination with insect-resistant transgenic crops for integrated pest management. It is in
this context that molecular techniques can be employed to detect different receptor sites,
and screening of the molecules for receptor specifi city, and mode of action. Functional
genomics offers the opportunity to acquire in-depth knowledge of the genetic makeup
and gene function of insect pests that may lead to the discovery of new processes that
could be the targets for novel chemistry. Advances in pest control are now being aided
through rapid synthesis of novel compounds using combinational chemistry, genomics,
proteomics, and molecular modeling. Combining genomics with high-throughput biochemical
screening and combinatorial chemical approaches to generate extensive arrays of
compounds for screening will lead to a range of new chemicals for pest control. Another
application of molecular biology is the development of novel strains of entomopathogenic
bacteria, fungi, nuclear polyhedrosis viruses, and nematodes. Genomic technologies
will allow investigation of some previously intractable resistance mechanisms to both
synthetic insecticides and biopesticides. The molecular techniques will be useful to understand
the nature of mutations and genetic processes such as gene amplifi cation, altered
gene transcription, and amino acid substitution. This in turn will lead to high-resolution
diagnostics for resistance alleles, in both homozygous and heterozygous forms, especially
for insect pests with multiple resistance mechanisms, or for resistance mechanisms not
amenable to biochemical assays. The evolution of insecticide-resistant insects also provides
evolutionary biologists an ideal model system for studying how new adaptations can
be rapidly acquired. There is, therefore, a great interest in the use of the tools of molecular
biology to develop new insecticide molecules and elucidate the mechanisms of resistance
to insecticides.