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Professor Bill Ballard will present on research which employs population cages to explore the potential for temporal habitat heterogeneity to explain the high levels of naturally occurring mtDNA variation in many species, including humans. The research employs population cages to explore the potential for temporal habitat heterogeneity to explain the high levels of naturally occurring mtDNA variation in many species, including humans. The study starts with four fly lines and focuses on the influence of diet in two. Notably, the dietary induced change in selection on Drosophila is greater than that triggered by the industrial revolution on the peppered moth, Biston betularia. Experimentally, it has been shown these data are driven by a V161L ND4 mutation in Complex I of the electron transport chain inducing relative differences in larval development time. To investigate the underlying mechanism transcriptome and metabolome studies were conducted. Unexpectedly, RNA-seq analyses detected 3160 significantly differentially expressed genes in female third instar larvae fed two diets. In collaboration, it is observed that strain D fed a high protein diet exhibits Akt phosphorylation suggesting insulin resistance. In comparison, the same strain upregulates Notch signaling when fed a high carbohydrate diet. Alternate mechanistic hypothesis are currently being investigated by manipulating dietary sugars including sorbitol and gluconic acid.