Acetaldehyde is a highly toxic intermediate generated by the enzymatic breakdown of ethanol (ethyl alcohol). Species that regularly consume ethanol, including both humans and the common fruit fly Drosophila melanogaster, rely on the enzyme aldehyde dehydrogenase (ALDH) for acetaldehyde detoxification. In the proposed work, a structural change in ALDH found in some populations of D. melanogaster, a species notable for its ability to thrive on fermenting fruit high in ethanol, will be studied. Initial results indicate that the altered ALDH has higher ability to detoxify acetaldehyde, but lower ability to detoxify other aldehydes, than the original enzyme. Thus the change is predicted to be beneficial in flies feeding on ethanol, but may be detrimental in the absence of ethanol. To test these predictions, survival and reproduction of flies with the original and altered ALDH will be compared on diets both containing and lacking ethanol. In addition, the catalytic properties of the two ALDH variants will be measured with a variety of biologically relevant aldehyde substrates.
By taking advantage of the powerful genetic tools available for Drosophila, the proposed work will give unique insight into the molecular basis of adaptation of an organism to its ecological niche. In addition, because ALDH has broadly similar structure and function in Drosophila as in humans, the results may shed light on the role of this enzyme in human health and disease.
