THE COMPLEX GENETICS OF LIFESPAN AND XENOBIOTIC RESISTANCE IN DROSOPHILA MELANOGASTER

Abstract

It is constantly observed that populations of species, like the DSPR, harbor considerable genetic variation for phenotypic traits. However, our understanding of the location, effect, and frequency of alleles that create variable genetic effects for each phenotypic trait is poorly understood and remains elusive. To tease apart the location, effect, and frequency of alleles with variable effects on phenotypic traits, this dissertation employs the DSPR, comprised of the elite model system Drosophila melanogaster, to investigate lifespan and xenobiotic resistance. Experiments on lifespan uncovered multiple quantitative trait loci (QTL) that harbor genes that shape lifespan and small sets of expression candidates. Moreover, as many expression studies have discovered, our expression candidates are enriched with antimicrobial defense genes that increase in expression with age, while electron transport chain genes decrease in expression with age. Exploring xenobiotic resistance we identify that Cyp28d1 and Cyp28d2 are likely to have variable effects on nicotine resistance, and Ugt86Dd is functionally important for nicotine resistance. Lastly, we discovered a complex 22bp deletion in Ugt86Dd that our data suggest is likely a causative variant within Ugt86Dd contributing variable effects on nicotine resistance in the DSPR. Our studies demonstrate the genetic architecture of lifespan is more complex than what is reported and lose of function variants may have an important role in creating variable effects on xenobiotic resistance.