Identifying Loci Contributing to Natural Variation in Xenobiotic Resistance in

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A striking feature of biology is that within populations there is substantial interindividual phenotypic variation for traits of biomedical significance. Some fraction of this variation is due to environmental factors, but for many traits segregating genetic differences contribute significantly to phenotypic variation. Elucidating those causative sequence changes that result in complex trait variation is of central importance to biology, and requires the coordinated use of multiple approaches. Here we employ a multi-level strategy to dissect genetic variation in caffeine resistance in Drosophila melanogaster, leveraging powerful genetic screening in a multiparental mapping panel, a genomewide association study, high-throughput RNA sequencing, and gene knockdowns using RNA interference. We identify several short genomic regions that collectively explain a substantial portion of the heritable variation for caffeine resistance, and find that several of these regions harbor members of known detoxification enzyme families. One such gene—Cyp12d1—shows increased expression on exposure to caffeine, and experimentally reducing gene expression leads to a reduction in caffeine resistance. We additionally show that variation in the number of copies of Cyp12d1 is positively associated with resistance. These compelling lines of evidence imply that structural variation at this gene causally contributes to xenobiotic resistance in Drosophila.

Vyšlo v časopise: Identifying Loci Contributing to Natural Variation in Xenobiotic Resistance in. PLoS Genet 11(11): e32767. doi:10.1371/journal.pgen.1005663
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005663

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