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Previous work showed that resistance to Bt toxin Cry1Ac, which is produced by transgenic cotton, can be conferred by mutations disrupting a cadherin protein that binds this Bt toxin in the larval midgut. However, the potential for epistatic interactions between the cadherin gene and other genes has received little attention. Here, we report evidence of epistasis conferring resistance to Cry1Ac in the cotton bollworm, <jats:italic>Helicoverpa armigera<\/jats:italic>, one of the world's most devastating crop pests. Resistance to Cry1Ac in strain LF256 originated from a field\u2010captured male and was autosomal, recessive, and 220\u2010fold relative to susceptible strain SCD. We conducted complementation tests for allelism by crossing LF256 with a strain in which resistance to Cry1Ac is conferred by a recessive allele at the cadherin locus <jats:italic>HaCad<\/jats:italic>. The resulting F<jats:sub>1<\/jats:sub> offspring were resistant, suggesting that resistance to Cry1Ac in LF256 is also conferred by resistance alleles at this locus. However, the <jats:italic>HaCad<\/jats:italic> amino acid sequence in LF256 lacked insertions and deletions, and did not differ consistently between LF256 and a susceptible strain. In addition, most of the cadherin alleles in LF256 were not derived from the field\u2010captured male. Moreover, Cry1Ac resistance was not genetically linked with the <jats:italic>HaCad<\/jats:italic> locus in LF256. Furthermore, LF256 and the susceptible strain were similar in levels of <jats:italic>HaCad<\/jats:italic> transcript, cadherin protein, and binding of Cry1Ac to cadherin. Overall, the results imply that epistasis between <jats:italic>HaCad<\/jats:italic> and an unknown second locus in LF256 yielded the observed resistance in the F<jats:sub>1<\/jats:sub> progeny from the complementation test. The observed epistasis has important implications for interpreting results of the F<jats:sub>1<\/jats:sub> screen used widely to monitor and analyze resistance, as well as the potential to accelerate evolution of resistance.<\/jats:p>","DOI":"10.1111\/eva.12598","type":"journal-article","created":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T15:09:27Z","timestamp":1516201767000},"page":"809-819","source":"Crossref","is-referenced-by-count":17,"title":["Epistasis confers resistance to Bt toxin Cry1Ac in the cotton bollworm"],"prefix":"10.1111","volume":"11","author":[{"given":"Meijing","family":"Gao","sequence":"first","affiliation":[{"name":"College of Plant Protection Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximeng","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Plant Protection Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihua","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Plant Protection Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce E.","family":"Tabashnik","sequence":"additional","affiliation":[{"name":"Department of Entomology University of Arizona  Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3456-3373","authenticated-orcid":false,"given":"Yidong","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Plant Protection Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/mec.13841"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.111.130971"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2583.2005.00563.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2011.02.006"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2016.07.008"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jip.2017.03.013"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126288"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1983-40632013000100015"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169115"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cois.2016.04.002"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.117.203059"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035658"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cropro.2014.06.019"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001248"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.8.3519"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005124"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.106.064550"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.4161\/gmcr.20539"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1190242"},{"key":"e_1_2_7_21_1","unstructured":"James C.(2016).Global Status of Commercialized Biotech\/GM Crops: 2016.ISAAA Brief No. 52. 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