|Splice form variant and amino acid changes in MDR49 confers DDT resistance in transgenic Drosophila.
|Year of Publication
|Seong, KMook, Sun, W, Clark, JM, Pittendrigh, BR
|2016 Mar 22
|Alternative Splicing, Amino Acid Sequence, Amino Acids, Animals, Animals, Genetically Modified, ATP Binding Cassette Transporter, Subfamily B, DDT, Drosophila melanogaster, Drosophila Proteins, Insecticide Resistance, Mutation, Open Reading Frames, Protein Isoforms, Sequence Analysis, RNA
The ATP-binding cassette (ABC) transporters represent a superfamily of proteins that have important physiological roles in both prokaryotes and eukaryotes. In insects, ABC transporters have previously been implicated in insecticide resistance. The 91-R strain of Drosophila melanogaster has been intensely selected with DDT over six decades. A recent selective sweeps analysis of 91-R implicated the potential role of MDR49, an ABC transporter, in DDT resistance, however, to date the details of how MDR49 may play a role in resistance have not been elucidated. In this study, we investigated the impact of structural changes and an alternative splicing event in MDR49 on DDT-resistance in 91-R, as compared to the DDT susceptible strain 91-C. We observed three amino acid differences in MDR49 when 91-R was compared with 91-C, and only one isoform (MDR49B) was implicated in DDT resistance. A transgenic Drosophila strain containing the 91-R-MDR49B isoform had a significantly higher LD50 value as compared to the 91-C-MDR49B isoform at the early time points (6 h to 12 h) during DDT exposure. Our data support the hypothesis that the MDR49B isoform, with three amino acid mutations, plays a role in the early aspects of DDT resistance in 91-R.
|PubMed Central ID