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Widespread use of insecticides has led to insecticide resistance in many populations of insects. In some populations, resistance has evolved to multiple pesticides. In  Drosophila melanogaster , resistance to multiple classes of insecticide is due to the overexpression of a single cytochrome P450 gene,  Cyp6g1 . Overexpression of  Cyp6g1  appears to have evolved in parallel in  Drosophila simulans , a sibling species of  D. melanogaster , where it is also associated with insecticide resistance. However, it is not known whether the ability of the CYP6G1 enzyme to provide resistance to multiple insecticides evolved recently in  D. melanogaster  or if this function is present in all  Drosophila  species. Here we show that duplication of the  Cyp6g1  gene occurred at least four times during the evolution of different  Drosophila  species, and the ability of CYP6G1 to confer resistance to multiple insecticides exists in  D. melanogaster  and  D. simulans  but not in  Drosophila willistoni  or  Drosophila virilis . In  D. virilis , which has multiple copies of  Cyp6g1 , one copy confers resistance to DDT and another to nitenpyram, suggesting that the divergence of protein sequence between copies subsequent to the duplication affected the activity of the enzyme. All orthologs tested conferred resistance to one or more insecticides, suggesting that CYP6G1 had the capacity to provide resistance to anthropogenic chemicals before they existed. Finally, we show that expression of  Cyp6g1  in the Malpighian tubules, which contributes to DDT resistance in  D. melanogaster , is specific to the  D. melanogaster – D. simulans  lineage. Our results suggest that a combination of gene duplication, regulatory changes and protein coding changes has taken place at the  Cyp6g1  locus during evolution and this locus may play a role in providing resistance to different environmental toxins in different  Drosophila  species.

plos one

Evolutionary Changes in Gene Expression, Coding Sequence and Copy-Number at the Cyp6g1 Locus Contribute to Resistance to Multiple Insecticides in Drosophila