Cost of a Naturally Occurring Two-Amino Acid Deletion in Cytochrome c Oxidase Subunit 7A in Drosophila simulans

This study aimed to determine whether a naturally occurring (Delta Trp85, Delta Val86) deletion from a protein subunit of cytochrome c oxidase (complex IV) influenced cytochrome c oxidase activity, mRNA expression levels of electron transport chain genes, and aspects of adult female fitness in the fly Drosophila simulans. We modeled the tertiary structure of D. simulans cox7A containing the deletion by homology to the bovine cox7A structure and predicted that it would decrease the function of complex IV. This prediction led to the hypothesis that flies with the deletion would have lower cytochrome c oxidase activity and higher levels of mRNA expression from cox7A. This result was observed, but unexpectedly, elevated levels of mRNA expression were also observed in genes encoding subunits of complexes I, III, and IV. Together these data suggest that the deletion causes a high bioenergetic cost to the organism. To investigate the predicted cost at a physiological level, we assayed aspects of adult female fitness. Starvation sensitivity but not feeding rate was significantly influenced by the two-amino acid deletion. Further, we observed that carbohydrate and protein levels but not lipid levels were higher in the mutant flies. Together, these data show that quaternary structure modeling and biochemistry can be used to link the genotype with the organismal phenotype.