title: Gene duplication in the major insecticide target site, Rdl, in Drosophila melanogaster.
abstract: The Resistance to Dieldrin gene, Rdl, encodes a GABA-gated chloride channel subunit that is targeted by cyclodiene and phenylpyrazole insecticides. The gene was first characterized in Drosophila melanogaster by genetic mapping of resistance to the cyclodiene dieldrin. The 4,000-fold resistance observed was due to a single amino acid replacement, Ala(301) to Ser. The equivalent change was subsequently identified in Rdl orthologs of a large range of resistant insect species. Here, we report identification of a duplication at the Rdl locus in D. melanogaster. The 113-kb duplication contains one WT copy of Rdl and a second copy with two point mutations: an Ala(301) to Ser resistance mutation and Met(360) to Ile replacement. Individuals with this duplication exhibit intermediate dieldrin resistance compared with single copy Ser(301) homozygotes, reduced temperature sensitivity, and altered RNA editing associated with the resistant allele. Ectopic recombination between Roo transposable elements is involved in generating this genomic rearrangement. The duplication phenotypes were confirmed by construction of a transgenic, artificial duplication integrating the 55.7-kb Rdl locus with a Ser(301) change into an Ala(301) background. Gene duplications can contribute significantly to the evolution of insecticide resistance, most commonly by increasing the amount of gene product produced. Here however, duplication of the Rdl target site creates permanent heterozygosity, providing unique potential for adaptive mutations to accrue in one copy, without abolishing the endogenous role of an essential gene.
authors: Department of Genetics and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC 3010, Australia. emily.remnant@sydney.edu.au
authors: Emily J
authors: EJ
authors: Remnant
authors: Robert T
authors: RT
authors: Good
authors: Joshua M
authors: JM
authors: Schmidt
authors: Christopher
authors: C
authors: Lumb
authors: Charles
authors: C
authors: Robin
authors: Phillip J
authors: PJ
authors: Daborn
authors: Philip
authors: P
authors: Batterham
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D056915:DNA Copy Number Variations; D004251:DNA Transposable Elements / Q000235:genetics; D004026:Dieldrin / Q000633:toxicity; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D015870:Gene Expression; D020043:Genes, Essential / Q000235:genetics; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D059645:Mutation Rate; D017354:Point Mutation; D011963:Receptors, GABA-A / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013696:Temperature
chemical_list: D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D007306:Insecticides; C082030:Rdl protein, Drosophila; D011963:Receptors, GABA-A; D004026:Dieldrin
references: Aust J Biol Sci. 1980 Mar;33(1):85-95
references: 7396809
references: PLoS Genet. 2011 Oct;7(10):e1002347
references: 22028677
references: Genet Res. 1991 Feb;57(1):17-21
references: 1904046
references: Arch Insect Biochem Physiol. 2010 Jun;74(2):81-90
references: 20513056
references: Annu Rev Entomol. 2007;52:231-53
references: 16925478
references: Insect Biochem Mol Biol. 1994 Apr;24(4):335-45
references: 8025556
references: PLoS Genet. 2012;8(12):e1003080
references: 23284287
references: J Econ Entomol. 2011 Apr;104(2):646-52
references: 21510217
references: J Econ Entomol. 2005 Aug;98(4):1305-10
references: 16156584
references: Philos Trans R Soc Lond B Biol Sci. 1998 Oct 29;353(1376):1685-93
references: 10021768
references: Biol Direct. 2011 Feb 18;6:11
references: 21333002
references: Pest Manag Sci. 2004 Dec;60(12):1157-62
references: 15578595
references: Annu Rev Entomol. 2001;46:545-71
references: 11112179
references: Insect Mol Biol. 2010 Mar;19 Suppl 2:141-53
references: 20482646
references: PLoS One. 2012;7(2):e30008
references: 22347367
references: Annu Rev Entomol. 1991;36:1-23
references: 2006866
references: Philos Trans R Soc Lond B Biol Sci. 1998 Oct 29;353(1376):1707-11
references: 10021771
references: Science. 2006 Dec 15;314(5806):1747-51
references: 17138868
references: Gene. 2009 Dec 15;448(2):124-33
references: 19555747
references: PLoS Genet. 2010 Jun 24;6(6):e1000998
references: 20585622
references: J Physiol. 1994 Aug 15;479 ( Pt 1):65-75
references: 7527461
references: J Mol Evol. 1999 May;48(5):615-24
references: 10198127
references: BMC Evol Biol. 2009 Aug 18;9:205
references: 19689787
references: Mol Biol Evol. 2007 Apr;24(4):1056-67
references: 17283366
references: Mol Gen Genet. 1998 Nov;260(2-3):165-75
references: 9862468
references: Nature. 1993 Jun 3;363(6428):449-51
references: 8389005
references: J Neurochem. 1992 Oct;59(4):1562-5
references: 1328525
references: Nature. 2012 Feb 08;482(7384):173-8
references: 22318601
references: J Neurosci. 2009 Apr 1;29(13):4287-92
references: 19339622
references: Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1957-61
references: 8095336
references: Nucleic Acids Res. 2005 Feb 24;33(4):e36
references: 15731329
references: Insect Mol Biol. 1993;2(3):149-54
references: 9087552
references: Insect Mol Biol. 2005 Apr;14(2):179-83
references: 15796751
references: Genome. 2010 Sep;53(9):688-97
references: 20924418
references: Mol Genet Genomics. 2001 Dec;266(4):556-63
references: 11810226
references: Nat Neurosci. 2008 Mar;11(3):354-9
references: 18223647
references: Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7209-13
references: 1651498
references: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3312-7
references: 17360644
references: Science. 2003 Nov 21;302(5649):1401-4
references: 14631042
references: Pest Manag Sci. 2011 Aug;67(8):886-90
references: 21538802
references: J Econ Entomol. 1990 Oct;83(5):1733-7
references: 2124226
references: Genome Res. 2009 Mar;19(3):452-9
references: 19196725
references: Genetics. 1991 Dec;129(4):1085-98
references: 1783293
references: J Econ Entomol. 2009 Feb;102(1):366-72
references: 19253656