|Title||A glycine insertion in the estrogen-related receptor (ERR) is associated with enhanced expression of three cytochrome P450 genes in transgenic Drosophila melanogaster.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Sun, W, M Valero, C, Seong, KMook, Steele, LD, Huang, I-T, Lee, C-H, Clark, JM, Qiu, X, Pittendrigh, BR|
|Keywords||Amino Acid Sequence, Animals, Animals, Genetically Modified, Conserved Sequence, Cytochrome P-450 Enzyme System, Drosophila melanogaster, Drosophila Proteins, Enzyme Induction, Female, Gene Expression, Glycine, Male, Molecular Sequence Data, Mutagenesis, Insertional, Phylogeny, Receptors, Estrogen|
Insecticide-resistant Drosophila melanogaster strains represent a resource for the discovery of the underlying molecular mechanisms of cytochrome P450 constitutive over-expression, even if some of these P450s are not directly involved in the resistance phenotype. For example, in select 4,4'-dichlorodiphenyltrichloroethane (DDT) resistant strains the glucocorticoid receptor-like (GR-like) potential transcription factor binding motifs (TFBMs) have previously been shown to be associated with constitutively differentially-expressed cytochrome P450s, Cyp12d1, Cyp6g2 and Cyp9c1. However, insects are not known to have glucocorticoids. The only ortholog to the mammalian glucocorticoid receptor (GR) in D. melanogaster is an estrogen-related receptor (ERR) gene, which has two predicted alternative splice isoforms (ERRa and ERRb). Sequencing of ERRa and ERRb in select DDT susceptible and resistant D. melanogaster strains has revealed a glycine (G) codon insertion which was only observed in the ligand binding domain of ERR from the resistant strains tested (ERR-G). Transgenic flies, expressing the ERRa-G allele, constitutively over-expressed Cyp12d1, Cyp6g2 and Cyp9c1. Only Cyp12d1 and Cyp6g2 were over-expressed in the ERRb-G transgenic flies. Phylogenetic studies show that the G-insertion appeared to be located in a less conserved domain in ERR and this insertion is found in multiple species across the Sophophora subgenera.
|Alternate Journal||PLoS One|
|PubMed Central ID||PMC4356566|