Nrf2/Maf-binding-site-containing functional Cyp6a2 allele is associated with DDT resistance in Drosophila melanogaster

Hua Wan, Yan Liu, Mei Li, Shunyi Zhu, Xianchun Li, Barry R. Pittendrigh, Xinghui Qiu

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)1048-1058
Number of pages11
JournalPest Management Science
Volume70
Issue number7
DOIs
StatePublished - 2014

Fingerprint

DDT (pesticide)
Drosophila melanogaster
binding sites
Alleles
Binding Sites
alleles
Terminal Repeat Sequences
Melanogaster
Genetic Promoter Regions
terminal repeat sequences
Maf Transcription Factors
Insecticide Resistance
Frameshift Mutation
DNA Transposable Elements
DDT
promoter regions
Sequence Deletion
3' Untranslated Regions
frameshift mutation
Cytochromes

Keywords

  • Cyp6a2
  • DDT resistance
  • Frameshift mutation
  • Long terminal repeat
  • Nrf2/Maf binding site
  • Overexpression

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Insect Science
  • Medicine(all)

Cite this

Nrf2/Maf-binding-site-containing functional Cyp6a2 allele is associated with DDT resistance in Drosophila melanogaster. / Wan, Hua; Liu, Yan; Li, Mei; Zhu, Shunyi; Li, Xianchun; Pittendrigh, Barry R.; Qiu, Xinghui.

In: Pest Management Science, Vol. 70, No. 7, 2014, p. 1048-1058.

Research output: Contribution to journalArticle

Wan, Hua ; Liu, Yan ; Li, Mei ; Zhu, Shunyi ; Li, Xianchun ; Pittendrigh, Barry R. ; Qiu, Xinghui. / Nrf2/Maf-binding-site-containing functional Cyp6a2 allele is associated with DDT resistance in Drosophila melanogaster. In: Pest Management Science. 2014 ; Vol. 70, No. 7. pp. 1048-1058.
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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 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.",
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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

Y1 - 2014

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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