Quantitative Trait Transcript Mapping for Drug Response in Drosophila melanogaster
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Date
2005-11-17
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Abstract
Here I used microarrays to identify genes that are activated or repressed by nicotine and caffeine in Drosophila melanogaster. I compared genotypes with differential resistance to each drug in order to select genes that may be involved in resistance to the drugs. Comparison of the genes differentially expressed by both drugs leads me to propose that there are common mechanisms of metabolic resistance to caffeine and nicotine, in particular cytochrome P-450-mediated mechanisms. Caffeine seems to have a more dramatic influence on gene expression than nicotine, in particular on expression of genes involved in energy metabolism. Next, I extended the studies on nicotine resistance to ask whether there are differences in response between two populations of Drosophila. The gene expression patterns of both populations were evaluated separately and in a combined analysis. Most of the differentially expressed genes were up-regulated by nicotine in both populations and in the combined analysis. The induced transcripts were mainly related to protein, nucleic acid, amino acid and energy metabolism, and response to stimulus and stress. Those findings suggest that amino acid and energy metabolism may be important biological processes affected by nicotine and be interesting targets for further investigation related to the nicotine response in Drosophila. The two populations displayed considerable differences in gene expression profiling that may be the result of the observed phenotypic variation for nicotine response between the two populations. Most of the differential expression induced by nicotine seems to be specific to the more resistant population. Finally, I focused on genes whose expression showed significant correlation with survival time on nicotine food. Using a regression approach, it was possible to map quantitative trait transcripts associated to nicotine response. Control expression of alkaline phosphatase and ornithine aminotransferase displayed significant correlation to survival time in drug food. They seem to be linked to regulation of GABA/glutamate neurotransmission and detoxification mechanisms, which ultimately counteracts the stimulatory effects of nicotine.
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quantitative trait transcript, Drosophila, microarray, caffeine, nicotine
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PhD
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Functional Genomics
