Transcript Genetic of Insecticide resistance

Genetic of Insecticide Resistance
Alvaro Romero
Department of Entomology
BIO508 -EVOLUTION
Fall-2006
University of Kentucky
Resistance-definition
“The inherited ability of a strain of some
organism to survive doses of a toxicant
that would kill the majority of individuals
in a normal population of the same
species” (WHO, 1957).
Resistance Mechanisms in Insects
Increased enzymatic detoxification
• Monooxygenase-mediated resistance (P450s)
• Esterases
• Glutathione S-transferases
P450
opm.phar.umich.edu/images/proteins/1e6e.gif
Target site insensitivity
• Voltage-gated ion channels
• Acetylcholinesterase
• Ligand-gated ion channels
Key Questions in Insecticide
Resistance
• Resistance phenotype controlled by one or more
genes?
• How many mutations are within resistance
genes?
• How many independent origins do they have in
the field population?
Ffrech-Constant, R. H. et al. (2004). The genetics and genomics of insecticide resistance. TRENDS in
Genetics. Vol. 20 (3): 163-170
How Many Resistance Genes are
Selected to Confer Resistance?
Lab populations
(Selection for several
resistant traits-polygenic)
Field populations under
intensive selection
(selection for rare mutationswith major effect- Monogenic).
ffrech-Constant, R. H. et al. (2004).
More than one gene in laboratoryselected populations
Genetics 130: 613-620
Single genes-examples
ffrech-Constant, R. H. et al. (2004).
Single genes with major effects… even in
complex multigene enzyme systems (P450)
Identification of an insecticide resistance gene via transcriptional
analysis using DNA microarray
ffrech-Constant, R. H. et al. (2004).
Paradigms (1)
Genes of major effect play a key role in
field–evolved resistance because intensity
of selection is extremely high
Simulation model
General conditions
• Empirical estimates of selection intensity in the field (nine species
examined)
• Six unlinked loci, each with two alleles
• Starting population: 10,000 individuals
• Individual’s genotype was estimated by summing genotypic effect
across alleles at each locus and across the six loci
• Populations were resistant when 50% of the individuals had tolerance
values greater than a threshold value that would kill 95% of individuals
with susceptible genotypes (G = 0)
Characteristic of six-locus models simulated
This is genotypic effect of resistant alleles
(Genotypic effect of susceptible alleles: 0)
Polygenic model
Effect of each allele is
Small and nearly equally
Intermediate model
Monogenic model
Effect of one allele (80% of
the total resistance)
is larger than the others
Initial frequency also varies: Alleles of smaller effect
Alleles of greater effect
Groeters and Tabashinik (2000).
High frequency
Low frequency
Results
Selection at 50% (weakest), 10% (weak), and 1% (strong)
Groeters and Tabashinik (2000).
Results
Resistance evolved faster
in model C and D (monogenic)
Groeters and Tabashinik (2000).
Paradigm (1)
• Genes of major effect play a key role in
field – evolved resistance because
intensity of selection is extremely high
Rebuttal
Major genes dominated responses to
selection for resistance across a wide
range of simulated selection intensities
Paradigm (2)
Monogenically-based field resistance, caused by
intensive field selection, is followed by the
appearance of polygenetic variation after
selection in the lab.
Intensive field selection …then…. weak laboratory selection
Intensive selection (10%) for 40
generations fixes the major and
intermediate alleles
Groeters and Tabashinik (2000).
Further weak selection
(50%) fixes the minor allele
(polygenetic resistance)
Weak field selection …then…. Strong laboratory selection
Weak selection (50%) for 40
generations fixes the major effect
allele (monogenetic resistance)
Groeters and Tabashinik (2000).
Further strong selection (10%)
fixes the intermediate and
eventually the minor allele
(polygenetic resistance)
Paradigm (2)
Monogenically-based field resistance, caused by intensive
field selection, is followed by the appearance of
polygenetic variation after selection in the lab.
Rebuttal
The situation may be more complex
The frequency of major and minor alleles
for resistance depends on the
population’s selection history and the
moment that genetic basis is studied.
Practical Implications of this Simulation
Model
• Use of intensive selection at the lab to mimic field
evolution may be invalid (there is a wide range of intensity
of selection in the field)
• Contribute to the investigation of more general
evolutionary phenomena of adaptation
• An excellent tool to study the ability of refuges to delay
the evolution of resistance
Refuge Strategy
Groups of susceptible individuals that are
not exposed to insecticides which then
mate resistant ones to keep a vulnerable
population
Refuge model
• Percentage of the population (r) avoid selection.
• Selection applied to the remaining (100-r) % of the
population
• Adults surviving selection and refuges were combined
randomly
• Refuge sizes of 10 and 25%
Resistant delay
# of generations for resistance to evolve with a refuge
Minus
# of generations for resistance to evolve without a refuge
Results-refuges
• Delay of resistance depends
mainly on selection intensity
but not by the distribution of
allelic effects among major and
minor loci
Low selection (50 and 10%), little
delay at a refuge rate of 10 and
25%
High selection (1%), a greater
delay, especially at a refuge rate
of 25%.
Groeters and Tabashinik (2000).