Dissertation Research: Pathway Analysis of Ethanol and Acetic Acid Detoxification in Drosophila

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0105085ClarkEthanol and acetic acid tolerance are highly positively correlated across populations of D. melanogaster and species of Drosophila. The non-independence of traits associated with different steps in the ethanol and acetic acid detoxification pathway underscores the need for a pathway analysis of ethanol and acetic acid tolerance. Analysis of this complete pathway was hindered by the fact that only ADH and aldehyde oxidase (ALDOX) could be studied at the biochemical and molecular levels, leaving the third step in the ethanol detoxification pathway, catalyzed by acetyl Co-A synthetase (AcCoAS), uncharacterized. Identification of AcCoAS from the complete genome sequence of D. melanogaster and recently developed molecular probes for the AcCoAS reaction now allow for a complete pathway analysis of ethanol and acetic acid tolerance. We hypothesize that selection for both tolerances operates on the entire detoxification pathway and will shape the patterns of variation and covariation between the three key enzymes in the pathway. A combination of techniques will be employed to quantify variation in and covariation between nucleotide sequence data, mRNA expression levels, enzyme activities and tolerance to both ethanol and acetic acid.The research funded by this Doctoral Dissertation Improvement Grant takes an evolutionary quantitative genetic approach to characterize the relationship between genetic variation and enzyme activity variation at all three steps in the pathway and the consequences of this variation on ethanol and acetic acid tolerance. The findings will be analyzed in the context of metabolic control theory and will allow us to make predictions about the genetic and biochemical responses to selection on organismal performance