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The gene encoding the insect nicotinic acetylcholine receptor (<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>) \u03b16 subunit, target of the bio\u2010insecticide spinosad, is one example of this and expands protein diversity via alternative splicing of mutually exclusive exons. Here, we show that spinosad resistance in the tomato leaf miner, <jats:italic>Tuta absoluta<\/jats:italic> is associated with aberrant regulation of splicing of <jats:italic>Ta<\/jats:italic>\u03b1<jats:italic>6<\/jats:italic> resulting in a novel form of insecticide resistance mediated by exon skipping. Sequencing of the \u03b16 subunit <jats:styled-content style=\"fixed-case\">cDNA<\/jats:styled-content> from spinosad selected and unselected strains of <jats:italic>T.\u00a0absoluta<\/jats:italic> revealed all <jats:italic>Ta<\/jats:italic>\u03b1<jats:italic>6<\/jats:italic> transcripts of the selected strain were devoid of exon 3, with comparison of genomic <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> revealing this is a result of exon skipping. Exon skipping cosegregated with spinosad resistance in survival bioassays, and functional characterization of this alteration using modified human <jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content> \u03b17, a model of insect \u03b16, demonstrated that exon 3 is essential for receptor function and hence spinosad sensitivity. <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> sequencing analyses suggested that exon skipping did not result from genetic alterations in intronic or exonic <jats:italic>cis<\/jats:italic>\u2010regulatory elements, but rather was associated with a single epigenetic modification downstream of exon 3a, and quantitative changes in the expression of <jats:italic>trans<\/jats:italic>\u2010acting proteins that have known roles in the regulation of alternative splicing. Our results demonstrate that the intrinsic capacity of the \u03b16 gene to generate transcript diversity via alternative splicing can be readily exploited during the evolution of resistance and identifies exon skipping as a molecular alteration conferring insecticide resistance.<\/jats:p>","DOI":"10.1111\/mec.13882","type":"journal-article","created":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T09:26:04Z","timestamp":1476696364000},"page":"5692-5704","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Insecticide resistance mediated by an exon skipping event"],"prefix":"10.1111","volume":"25","author":[{"given":"Madeleine","family":"Berger","sequence":"first","affiliation":[{"name":"Rothamsted Research Harpenden AL5 2JQ UK"},{"name":"School of Life Sciences University of Nottingham Nottingham NG7 2RD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alin Mirel","family":"Puinean","sequence":"additional","affiliation":[{"name":"Rothamsted Research Harpenden AL5 2JQ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Randall","sequence":"additional","affiliation":[{"name":"College of Life and Environmental Sciences Biosciences University of Exeter Penryn Campus Penryn Cornwall TR10 9FE UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph T.","family":"Zimmer","sequence":"additional","affiliation":[{"name":"College of Life and Environmental Sciences Biosciences University of Exeter Penryn Campus Penryn Cornwall TR10 9FE UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wellington M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Departamento de Agronomia\u2014(Entomologia) Universidade Federal Rural de Pernambuco 52171\u2010900 Recife PE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Bielza","sequence":"additional","affiliation":[{"name":"Departamento de Producci\u00f3n Vegetal Universidad Polit\u00e9cnica de Cartagena Paseo Alfonso XIII 48 Cartagena 30203 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M.","family":"Field","sequence":"additional","affiliation":[{"name":"Rothamsted Research Harpenden AL5 2JQ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hughes","sequence":"additional","affiliation":[{"name":"Rothamsted Research Harpenden AL5 2JQ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Mellor","sequence":"additional","affiliation":[{"name":"School of Life Sciences University of Nottingham Nottingham NG7 2RD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keywan","family":"Hassani\u2010Pak","sequence":"additional","affiliation":[{"name":"Rothamsted Research Harpenden AL5 2JQ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert A. 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