Résumé
Gene copy-number variations are widespread in natural populations, but
investigating their phenotypic consequences requires contemporary
duplications under selection. Such duplications have been found at the
ace-1 locus (encoding the organophosphate and carbamate insecticides’
target) in the mosquito Anopheles gambiae (the major malaria vector);
recent studies have revealed their intriguing complexity, consistent with
the involvement of various numbers and types (susceptible or resistant to
insecticide) of copies. We used an integrative approach, from genome to
phenotype level, to investigate the influence of duplication architecture
and gene-dosage on mosquito fitness. We found that both heterogeneous
(i.e., one susceptible and one resistant ace-1 copy) and homogeneous
(i.e., identical resistant copies) duplications segregated in field
populations. The number of copies in homogeneous duplications was variable
and positively correlated with acetylcholinesterase activity and
resistance level. Determining the genomic structure of the duplicated
region revealed that, in both types of duplication, ace-1 and 11 other
genes formed tandem 203kb amplicons. We developed a diagnostic test for
duplications, which showed that ace-1 was amplified in all 173 resistant
mosquitoes analyzed (field-collected in several African countries), in
heterogeneous or homogeneous duplications. Each type was associated with
different fitness trade-offs: heterogeneous duplications conferred an
intermediate phenotype (lower resistance and fitness costs), whereas
homogeneous duplications tended to increase both resistance and fitness
cost, in a complex manner. The type of duplication selected seemed thus to
depend on the intensity and distribution of selection pressures. This
versatility of trade-offs available through gene duplication highlights
the importance of large mutation events in adaptation to environmental
variation. This impressive adaptability could have a major impact on
vector control in Africa.