insecticides, widespread use of pyrethroids to target arthropod pests has resulted in
significant evolved resistance, increasingly rendering these chemicals ineffective as
treatments against pests that affect public health and food security. What is known
from the study of resistance in pest insects can be used to inform our understanding
of effects in nontarget invertebrates.
4.1.1 Pest Insects
A detailed review of pyrethroid resistance in pest insects is beyond the scope of the
present work but has been reviewed extensively elsewhere [52–55]. The strength of
the pesticide selective pressure is a function of dose and potency [100]. In general,
low level, sublethal pesticide exposures can drive a polygenic adaptation, potentially
involving adaptation in many genes of small effect to create a resistant phenotype.
Acute, lethal exposures instead drive adaptive responses outside the phenotypic
response range distribution of the population, much more likely to result in the
selection of small changes in genes of large effect (e.g., a single nucleotide polymorphism (SNP) leading to an amino acid base pair substitution that prevents
binding in the target site) [see Ffrench-Constant et al. [101] for a discussion]. It is
clear that pyrethroids are capable of acting as strong selective forces that drive
evolution in pests over short timescales. A variety of mechanisms underlie pesticide
resistance phenotypes, again related to dose and potency, but they can generally be
classified into two main groups: those that reduce the amount of the pesticide able to
reach the target site and those that modify the target site to reduce its sensitivity to the
pesticide [102]. Some of the most frequently described adaptive changes include
metabolic resistance (e.g., gene duplications, cis or trans gene mutations leading to
constitutive up- or downregulation of genes responsible for pesticide metabolism)
and target site insensitivity (mutations that prevent or reduce pyrethroid binding
affinity at the target site) [55]. Mutations that lead to target site insensitivity are also
sometimes referred to knockdown resistance (kdr) mutations, because they prevent
the “knockdown” phenotype by reducing target site binding affinity. Given that the
primary target site for pyrethroids (the Vgsc) is essential for arthropod nervous
systems, its functional constraints limit the non-synonymous base pair substitutions
that produce a sufficiently functional target protein while conferring resistance. Thus
it is even common to see the same target site mutations arise across many arthropod
species independently, providing examples of convergent evolution [103]. It is also
not uncommon to observe some adaptive mechanisms of resistance that confer crossresistance to a several different classes of insecticide at once. These types of
resistance are typically modulated by metabolic resistance mechanisms such as
cytochrome P450s, esterases, and glutathione S-transferases [104, 105]; target site
insensitivity can also confer cross-resistance if pesticide classes have the same target
sites (e.g., pyrethroids and DDT, organophosphates and carbamates) [106].
Recently, epigenetic changes in resistant insects have also been increasingly
suggested as players in adaptive resistance [91]. Epigenetic control of a trait affecting fitness may even allow for adaptation to occur at a quicker rate (see Oppold and
The Ecological and Evolutionary Implications of Pyrethroid Exposure: A New. . .
119
significant evolved resistance, increasingly rendering these chemicals ineffective as
treatments against pests that affect public health and food security. What is known
from the study of resistance in pest insects can be used to inform our understanding
of effects in nontarget invertebrates.
4.1.1 Pest Insects
A detailed review of pyrethroid resistance in pest insects is beyond the scope of the
present work but has been reviewed extensively elsewhere [52–55]. The strength of
the pesticide selective pressure is a function of dose and potency [100]. In general,
low level, sublethal pesticide exposures can drive a polygenic adaptation, potentially
involving adaptation in many genes of small effect to create a resistant phenotype.
Acute, lethal exposures instead drive adaptive responses outside the phenotypic
response range distribution of the population, much more likely to result in the
selection of small changes in genes of large effect (e.g., a single nucleotide polymorphism (SNP) leading to an amino acid base pair substitution that prevents
binding in the target site) [see Ffrench-Constant et al. [101] for a discussion]. It is
clear that pyrethroids are capable of acting as strong selective forces that drive
evolution in pests over short timescales. A variety of mechanisms underlie pesticide
resistance phenotypes, again related to dose and potency, but they can generally be
classified into two main groups: those that reduce the amount of the pesticide able to
reach the target site and those that modify the target site to reduce its sensitivity to the
pesticide [102]. Some of the most frequently described adaptive changes include
metabolic resistance (e.g., gene duplications, cis or trans gene mutations leading to
constitutive up- or downregulation of genes responsible for pesticide metabolism)
and target site insensitivity (mutations that prevent or reduce pyrethroid binding
affinity at the target site) [55]. Mutations that lead to target site insensitivity are also
sometimes referred to knockdown resistance (kdr) mutations, because they prevent
the “knockdown” phenotype by reducing target site binding affinity. Given that the
primary target site for pyrethroids (the Vgsc) is essential for arthropod nervous
systems, its functional constraints limit the non-synonymous base pair substitutions
that produce a sufficiently functional target protein while conferring resistance. Thus
it is even common to see the same target site mutations arise across many arthropod
species independently, providing examples of convergent evolution [103]. It is also
not uncommon to observe some adaptive mechanisms of resistance that confer crossresistance to a several different classes of insecticide at once. These types of
resistance are typically modulated by metabolic resistance mechanisms such as
cytochrome P450s, esterases, and glutathione S-transferases [104, 105]; target site
insensitivity can also confer cross-resistance if pesticide classes have the same target
sites (e.g., pyrethroids and DDT, organophosphates and carbamates) [106].
Recently, epigenetic changes in resistant insects have also been increasingly
suggested as players in adaptive resistance [91]. Epigenetic control of a trait affecting fitness may even allow for adaptation to occur at a quicker rate (see Oppold and
The Ecological and Evolutionary Implications of Pyrethroid Exposure: A New. . .
119