TY - JOUR
T1 - Nrf2/Maf-binding-site-containing functional Cyp6a2 allele is associated with DDT resistance in Drosophila melanogaster
AU - Wan, Hua
AU - Liu, Yan
AU - Li, Mei
AU - Zhu, Shunyi
AU - Li, Xianchun
AU - Pittendrigh, Barry R.
AU - Qiu, Xinghui
PY - 2014/7
Y1 - 2014/7
N2 - 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 Drosophilamelanogaster, how Cyp6a2 is regulated and whether its overproduction confers DDT resistance remain elusive. RESULTS: Molecular analysis identified five Cyp6a2 alleles (Cyp6a2Canton-S-1, Cyp6a2Canton-S-2, Cyp6a291-C, Cyp6a291-R and Cyp6a2Wisconsin-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 (Cyp6a291-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 Cyp6a2allele is associated with DDT resistance in the D.melanogaster strains under study.
AB - 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 Drosophilamelanogaster, how Cyp6a2 is regulated and whether its overproduction confers DDT resistance remain elusive. RESULTS: Molecular analysis identified five Cyp6a2 alleles (Cyp6a2Canton-S-1, Cyp6a2Canton-S-2, Cyp6a291-C, Cyp6a291-R and Cyp6a2Wisconsin-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 (Cyp6a291-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 Cyp6a2allele is associated with DDT resistance in the D.melanogaster strains under study.
KW - Cyp6a2
KW - DDT resistance
KW - Frameshift mutation
KW - Long terminal repeat
KW - Nrf2/Maf binding site
KW - Overexpression
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U2 - 10.1002/ps.3645
DO - 10.1002/ps.3645
M3 - Article
C2 - 24038867
SN - 1526-498X
VL - 70
SP - 1048
EP - 1058
JO - Pest management science
JF - Pest management science
IS - 7
ER -