title: Functional and evolutionary consequences of pyrethroid resistance mutations in S6 transmembrane segments of a voltage-gated sodium channel.
abstract: Pyrethroids are a class of voltage-dependent sodium channel modifiers widely used as insecticides for control of disease vectors and agricultural pests. Many insect populations have developed resistance to pyrethroids linked to nervous system insensitivity and structural mutations in neuronal sodium channels. Pyrethroid resistant strains of the moth Heliothis virescens carry single point mutations leading to amino acid substitutions in either transmembrane segment I-S6 (V421M) or II-S6 (L1029H) of the para-homologous sodium channel. We analyzed the consequences of V421M and L1029H mutations constructed in the Drosophila para sodium channel heterologously expressed in Xenopus oocytes, and found that both mutations confer channel insensitivity to permethrin, with the L1029H mutation having a more pronounced effect. Both mutations also modify the intrinsic voltage-dependent gating properties of the channel, but L1029H less so than V421M. These results suggest that mutation V421M exacts a higher fitness cost than L1029H, providing a plausible explanation for genetic succession observed in field strains, where V421M was replaced by L1029H during the past decade.
authors.affiliation: Department of Entomology, University of California at Riverside, Riverside, California, 92521, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: Y
authors.initials: Y
authors.lastname: Park
authors.forename: M E
authors.initials: ME
authors.lastname: Adams
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D003001:Cloning, Molecular; D004331:Drosophila melanogaster / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D006793:Houseflies / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009036:Moths / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D026023:Permethrin; D017354:Point Mutation; D017433:Protein Structure, Secondary; D011722:Pyrethrins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D011722:Pyrethrins; D011994:Recombinant Proteins; D015222:Sodium Channels; D026023:Permethrin