title: Cis-acting mutation and duplication: History of molecular evolution in a P450 haplotype responsible for insecticide resistance in Culex quinquefasciatus.
abstract: A cytochrome P450 gene, Cyp9m10, is more than 200-fold overexpressed in a pyrethroid resistant strain of Culex quinquefasciatus, JPal-per. The haplotype of this strain contains two copies of Cyp9m10 resulted from recent tandem duplication. In this study, we discovered and isolated a Cyp9m10 haplotype closely related to this duplicated Cyp9m10 haplotype from JHB, a strain used for the recent genome project for this mosquito species. The isolated haplotype (JHB-NIID-B haplotype) shared the same insertion of a transposable element upstream of the coding region with JPal-per strain but not duplicated. The JHB-NIID-B haplotype was considered to have diverged from the JPal-per lineage just before the duplication event. Cyp9m10 was moderately overexpressed in larvae with the JHB-NIID-B haplotype. The overexpressions in JHB-NIID-B and JPal-per haplotypes were developmentally regulated in similar pattern indicating both haplotypes share a common cis-acting mutation responsible for the overexpressions. The isolated moderately overexpressed haplotype conferred resistance, however, its efficacy was relatively small. We hypothesized that the first cis-acting mutation modified the consequence of the subsequent duplication in JPal-per lineage to confer stronger phenotypic effect than that if it occurred before the first cis-acting mutation.
authors.affiliation: Department of Nanobiology, Graduate School of Advanced Integration Science, Chiba University, 1-33 Yayoi, Inage-ku, Chiba 263-8522, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Itokawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Komagata
authors.forename: Shinji
authors.initials: S
authors.lastname: Kasai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Masada
authors.forename: Takashi
authors.initials: T
authors.lastname: Tomita
mesh_terms: D000349:Africa; D000818:Animals; D001208:Asia; D001483:Base Sequence; D003465:Culex / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D016172:DNA Fingerprinting; D019143:Evolution, Molecular; D020440:Gene Duplication; D015870:Gene Expression; D056726:Genetic Association Studies; D049750:Genome, Insect; D006239:Haplotypes; D007303:Insect Vectors / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology; D007814:Larva / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D026023:Permethrin / Q000494:pharmacology*; D011157:Population Dynamics; D016415:Sequence Alignment
chemical_list: D007306:Insecticides; D026023:Permethrin; D003577:Cytochrome P-450 Enzyme System