title: The nicotinic acetylcholine receptor gene family of the malaria mosquito, Anopheles gambiae.
abstract: Nicotinic acetylcholine receptors (nAChRs) mediate fast cholinergic synaptic transmission in the insect nervous system and are targets of widely selling insecticides. We have identified the nAChR gene family from the genome of the malaria mosquito vector, Anopheles gambiae, to be the second complete insect nAChR gene family described following that of Drosophila melanogaster. Like Drosophila, Anopheles possesses 10 nAChR subunits with orthologous relationships evident between the two insects. Interestingly, the Anopheles orthologues of Dbeta2 and Dbeta3 possess the vicinal cysteines that define alpha subunits. As with Dalpha4 and Dalpha6, the Anopheles orthologues are alternatively spliced at equivalent exons. Reverse transcription-polymerase chain reaction analysis shows that RNA A-to-I editing sites conserved between Dalpha6 of Drosophila and alpha7-2 of the tobacco budworm, Heliothis virescens, are not shared with the equivalent nAChR subunit of Anopheles. Indeed, RNA-editing sites identified in functionally significant regions of Dbeta1, Dalpha5, and Dalpha6 are not conserved in the mosquito orthologues, indicating considerable divergence of RNA molecules targeted for editing within the insect order Diptera. These findings shed further light on the diversity of nAChR subunits and may present a useful basis for the development of improved malaria control agents by enhancing our understanding of a validated mosquito insecticide target.
authors.affiliation: MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, United Kingdom.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Jones
authors.forename: Marta
authors.initials: M
authors.lastname: Grauso
authors.forename: David B
authors.initials: DB
authors.lastname: Sattelle
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000235:genetics*; D002874:Chromosome Mapping; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000235:genetics; D023061:Gene Order; D016678:Genome; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D021122:Protein Subunits / Q000235:genetics; D017393:RNA Editing; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029721:Drosophila Proteins; D021122:Protein Subunits; D011978:Receptors, Nicotinic