Experimental Selection for Drosophila Survival in Extremely High O2 Environments |
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Authors: | Huiwen W. Zhao Dan Zhou Victor Nizet Gabriel G. Haddad |
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Affiliation: | 1. Divisions of Respiratory Medicine, Infectious Disease and Pharmacology and Drug Discovery, Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.; 2. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, United States of America.; 3. Rady Children''s Hospital, San Diego, California, United States of America.;Centre for Genomic Regulation (CRG), Universitat Pompeu Fabra, Spain |
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Abstract: | Although oxidative stress is deleterious to mammals, the mechanisms underlying oxidant susceptibility or tolerance remain to be elucidated. In this study, through a long-term laboratory selection over many generations, we generated a Drosophila melanogaster strain that can live and reproduce in very high O2 environments (90% O2), a lethal condition to naïve flies. We demonstrated that tolerance to hyperoxia was heritable in these flies and that these hyperoxia-selected flies exhibited phenotypic differences from naïve flies, such as a larger body size and increased weight by 20%. Gene expression profiling revealed that 227 genes were significantly altered in expression and two third of these genes were down-regulated. Using a mutant screen strategy, we studied the role of some altered genes (up- or down-regulated in the microarrays) by testing the survival of available corresponding P-element or UAS construct lines under hyperoxic conditions. We report that down-regulation of several candidate genes including Tropomyosin 1, Glycerol 3 phosphate dehydrogenase, CG33129, and UGP as well as up-regulation of Diptericin and Attacin conferred tolerance to severe hyperoxia. In conclusion, we identified several genes that were not only altered in hyperoxia-selected flies but we also prove that these play an important role in hyperoxia survival. Thus our study provides a molecular basis for understanding the mechanisms of hyperoxia tolerance. |
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