Method of proof and evidences for the concept that mitochondrial genome is a thrifty genome

A hypothesis that mitochondrial genome itself is the thrifty genome has been advanced, as both its mutation, or quality, and amount in the peripheral blood, or quantity, are found to have close relationship to diabetes mellitus, or more specifically insulin resistance. Mere presence of relationship, however, does not establish cause-effect relation. Usually a genetic 'cause' is established, when a knockout of putative gene produces disease phenotype. However, absence of mitochondrial genome is incompatible with life. Here the argument advanced by Bradford Hill was applied to the proof of a hypothesis, as most of the data are from epidemiological observations; it is biologically plausible that both mtDNA quality and quantity are related to insulin resistance. The relationship had enough strength of association, dose-response relation, and consistency of relationship. Temporally association, decrease of mtDNA content preceding onset of diabetes, was also observed. Good hypothesis generates many predictions, which could be verified experimentally and which is biologically plausible.