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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 LD 50  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 .

Splice form variant and amino acid changes in MDR49 confers DDT resistance in transgenic Drosophila