Hua Wan1, Yan Liu, Mei Li, Shunyi Zhu, Xianchun Li, Barry R Pittendrigh, Xinghui Qiu. 1. State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
Abstract
BACKGROUND: Increased insecticide detoxification mediated by cytochrome P450s is a common mechanism of insecticide resistance. Although Cyp6a2 has been observed to be overexpressed in many 4,4'-dichlorodiphenyltrichloroethane (DDT)-resistant strains of Drosophila melanogaster, how Cyp6a2 is regulated and whether its overproduction confers DDT resistance remain elusive. RESULTS: Molecular analysis identified five Cyp6a2 alleles (Cyp6a2(Canton) (-S-1) , Cyp6a2(Canton) (-S-2) , Cyp6a2(91-C) , Cyp6a2(91-R) and Cyp6a2(Wisconsin) (-) (WD) ) from four D. melanogaster strains, notably differing in the presence or absence of an intact Nrf2/Maf (a transcription factor) binding site in the 5'-promoter core region, a 'G1410' frameshift deletion mutation in the heme-binding region and a long terminal repeat (LTR) of transposable element 17.6 in the 3'-untranslated region (UTR). Linkage analysis confirmed that DDT resistance was genetically linked to a Nrf2/Maf-binding-site-containing, LTR-lacking functional allele of Cyp6a2 (Cyp6a2(91-R) ). The qRT-PCR results showed that overexpression of functional Cyp6a2 was consistently associated with DDT resistance. Luciferase reporter gene assays revealed that an intact Nrf2/Maf binding site in the 5'-promoter core region enhanced the constitutive transcription of Cyp6a2. CONCLUSION: The results suggest that the Nrf2/Maf binding-site-containing functional Cyp6a2 allele is associated with DDT resistance in the D. melanogaster strains under study.
BACKGROUND: Increased insecticide detoxification mediated by cytochrome P450s is a common mechanism of insecticide resistance. Although Cyp6a2 has been observed to be overexpressed in many 4,4'-dichlorodiphenyltrichloroethane (DDT)-resistant strains of Drosophila melanogaster, how Cyp6a2 is regulated and whether its overproduction confers DDT resistance remain elusive. RESULTS: Molecular analysis identified five Cyp6a2 alleles (Cyp6a2(Canton) (-S-1) , Cyp6a2(Canton) (-S-2) , Cyp6a2(91-C) , Cyp6a2(91-R) and Cyp6a2(Wisconsin) (-) (WD) ) from four D. melanogaster strains, notably differing in the presence or absence of an intact Nrf2/Maf (a transcription factor) binding site in the 5'-promoter core region, a 'G1410' frameshift deletion mutation in the heme-binding region and a long terminal repeat (LTR) of transposable element 17.6 in the 3'-untranslated region (UTR). Linkage analysis confirmed that DDT resistance was genetically linked to a Nrf2/Maf-binding-site-containing, LTR-lacking functional allele of Cyp6a2 (Cyp6a2(91-R) ). The qRT-PCR results showed that overexpression of functional Cyp6a2 was consistently associated with DDT resistance. Luciferase reporter gene assays revealed that an intact Nrf2/Maf binding site in the 5'-promoter core region enhanced the constitutive transcription of Cyp6a2. CONCLUSION: The results suggest that the Nrf2/Maf binding-site-containing functional Cyp6a2 allele is associated with DDT resistance in the D. melanogaster strains under study.
Authors: Vanessa Bottino-Rojas; Octavio A C Talyuli; Luana Carrara; Ademir J Martins; Anthony A James; Pedro L Oliveira; Gabriela O Paiva-Silva Journal: J Biol Chem Date: 2018-04-23 Impact factor: 5.157
Authors: Joshua M Schmidt; Paul Battlay; Rebecca S Gledhill-Smith; Robert T Good; Chris Lumb; Alexandre Fournier-Level; Charles Robin Journal: Genetics Date: 2017-09-21 Impact factor: 4.562
Authors: Weilin Sun; M Carmen Valero; Keon Mook Seong; Laura D Steele; I-Ting Huang; Chien-Hui Lee; John M Clark; Xinghui Qiu; Barry R Pittendrigh Journal: PLoS One Date: 2015-03-11 Impact factor: 3.240