Dissertation abstract

__The vitamin folic acid is a cofactor for several biochemical reactions, including nucleotide synthesis and metabolism of certain amino acids. Folate deficiency can lead to anemia, cancer, and neurological disorders, but the mechanisms of these effects remain unclear. The fruitfly, Drosophila melanogaster, is a potentially useful model for studying the mechanisms of folate's biomedical effects. However, the current literature disagrees on whether folate is a vitamin for insects, and lacks information on the dose-response of insect biochemistry, physiology and fitness to dietary folate. This dissertation examined folic acid in relation to endosymbionts, growth, and metabolites of the fruit fly. The first study showed that fruit flies consuming diets lacking folic acid received sufficient folates from symbionts to allow for normal development, and suggested that symbionts only provided folates to the host when folate was absent from the diet. The second study examined how fruit flies respond to a wide range of dietary folic acid levels. Body folate levels of late-stage larvae were nearly homeostatically-regulated despite huge variation in dietary folate levels; however, flies on very low folate diets were less likely to pupate and developed at normal rates. When reared for a second generation on these diets, larvae on the very low folate diets were more viable and retained the faster developmental and growth rates seen in the first generation. Low folate in the adult diet suppressed female fecundity. Results of the third study showed that folate is needed for DNA synthesis in fruit flies, but not for some single-carbon cycle reactions for which it is needed in mammals. The final study explored affects on growth and development caused by diets varying in folic acid and choline, a related nutrient, in so-called methylation diets. This study showed that fruit flies, unlike mammals, survive well on diets low in methyl-donors. In summary, while folate functions in fruit flies overlap with mammals; endosymbionts allow fruit flies to fare better when dietary folic acid is low, and flies may utilize additional metabolic pathways to accomplish functions that in mammals are folate-dependent.