title: Aldehyde oxidase is coamplified with the World's most common Culex mosquito insecticide resistance-associated esterases.
abstract: The evolution and spread of insecticide resistance is an important factor in human disease prevention and crop protection. The mosquito Culex quinquefasciatus is the main vector of the disease filariasis and a member of a species complex which is a common biting nuisance worldwide. The common insecticide resistance mechanism in this species involves germline amplification of the esterases estalpha21 and estbeta21. This amplification has arisen once and rapidly spread worldwide. Less common and more variable resistance phenotypes involve coamplification of estalpha3 and estbeta1, or individual amplification of a single estbeta1, different alleles of the same estalpha and estbeta gene loci. Estalpha21 and estbeta21 are on the same large fragment of amplified DNA (amplicon) 2.7 kb apart. We have now shown that this amplicon contains another full-length gene immediately 5' of estalpha21 which codes for a molybdenum-containing hydroxylase, with highest homology to aldehyde oxidase (AO) from other organisms. The full-length putative AO gene is not present on the estalpha3/estbeta1 or estbeta1 amplicons, but multiple truncated 5' ends of this gene are present around the presumed estalpha3/estbeta1 amplicon breakpoint. Polymerase chain reaction (PCR) analysis of insecticide-susceptible genomic DNA demonstrated that a different allele of the putative AO gene in its non-amplified form is immediately 5' of estalpha. The 'AO' gene on the estalpha21/estbeta21 amplicon is expressed and resistant insects have greater AO activity. This AO activity is sensitive to inhibition by an aldehyde-containing herbicide and pesticide. This enzyme may confer a selective advantage to these insects in the presence of insecticide, as AO in mammals is believed to be important in the detoxification process of several environmental pollutants.
authors.affiliation: School of Biosciences, University of Wales, Cardiff, UK. sabjh@cardiff.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Hemingway
authors.forename: M
authors.initials: M
authors.lastname: Coleman
authors.forename: M
authors.initials: M
authors.lastname: Paton
authors.forename: L
authors.initials: L
authors.lastname: McCarroll
authors.forename: A
authors.initials: A
authors.lastname: Vaughan
authors.forename: D
authors.initials: D
authors.lastname: Desilva
mesh_terms: D042931:Aldehyde Oxidase; D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D000818:Animals; D015139:Blotting, Southern; D003465:Culex / Q000201:enzymology* / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D019143:Evolution, Molecular; D005784:Gene Amplification; D006801:Humans; D007305:Insecticide Resistance / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D000445:Aldehyde Oxidoreductases; D042931:Aldehyde Oxidase