Lanno, S. M. (2020). The Genetic Basis of Evolved Toxin Resistance in Insects: Insights from Drosophila sechellia. Retrieved from https://doi.org/10.14418/wes01.3.113
Our understanding of the genetic basis of adaptation is still evolving. A significant example of natural selection at work resulting in adaptive phenotypic changes is the evolution of insecticide resistance. The work presented in this thesis takes advantage of an interesting case study investigating the genetic basis of a recently acquired adaptive trait in Drosophila sechellia, a dietary specialist fruit fly that has evolved to overcome the toxic secondary defense compounds produced by the fruit of its host plant, Morinda citrifolia. I begin by examining the potential roles of common detoxification gene families routinely involved in evolved toxin resistance: cytochrome P450s, glutathione-S-transferases, and esterases. In order to further identify candidate resistance genes, I employ a functional genomics approach to measure genome-wide gene expression in D. sechellia and closely related sister species D. melanogaster and D. simulans upon exposure to toxins and chemicals found in Morinda fruit. Taking advantage of genetic and genomic tools in D. melanogaster, I use RNA interference to functionally test candidate resistance genes with bioassays to measure differences in survival upon toxin exposure. This work led to the discovery of specific genes underlying loci implicated in this resistance trait as well as a family of genes representing a novel route to evolve toxin resistance. Esterases were found to specifically alter toxin resistance in D. sechellia and the Esterase-6 gene was identified as both significantly differentially expressed and shown to functionally alter resistance phenotypes. Additionally, this work identified genes from the enigmatic Osiris family as important mediators of toxin resistance. Osiris 6 (Osi6), Osi7, and Osi8 were observed to alter sensitivity not only in the pairwise relationship between D. sechellia and its host plant toxins, but subsequent research using metagenomic analyses and functional genetics indicates these genes can also influence resistance to commercial insecticides. The findings presented in this thesis have potential to address global problems concerning insect pest management affecting both crop protection and disease vector control.