This is due to the enormous diversity of virus types, ranging from those that produce very small virions, less than 20 nm in diameter consisting of a single-stranded genome of 2 kbp and protein coat, to those with large and complex enveloped virions, 300 to greater than 1,000 nm in diameter, containing fifty or more proteins with double-stranded DNA genomes ranging from 200 to greater than 1,000 kbp. Polioviruses and parvoviruses are examples of the former, whereas poxviruses, iridoviruses, and mimiviruses are examples of the latter. This diversity suggests that unlike organisms, viruses are polyphyletic, with many, if not most types having originated independently. Complicating the evolutionary history of viruses is the evidence that many of the most complex types evolved by acquiring and exchanging genes with their hosts as they evolved. For these reasons, the highest taxonomic classification for the thousands of recognized viral species is at the level of the family, of which there are currently about seventy. The present and potential discrepancies between studies underline the continuing challenges of studies with different populations with different characteristics and pathophysiological and life-style related characteristics that may modify the effects of the examined gene variants. Our findings lend further support to the involvement of serotonin, noradrenaline and dopamine in energy and glucose homeostasis, and hence on the risk of obesity and T2D, in particular when combined genotype associations are explored. The results underscore the need for additional research in order to replicate the results and to identify the complex interplay between the examined psychophysiological genes that may further characterize their functionality in energy homeostasis. Bmi-1 is also critical for neural stem cell self-renewal. Bmi-1 was also recently shown to be a target of miR-128a in glioblastoma. Mitochondria have maintained a core set of genes that encode essential proteins in the ETC. Nonsynonymous mutations in these genes have the potential to affect the ETC, ROS production and longevity in a way that is dependent upon calorie restriction and/or calorie over-consumption. Throughout the last 150 years there have been dramatic extremes in per capita caloric intake. For example, during the Great Depression many individuals throughout North America were under extremely restricted caloric intake. In more recent decades there has been an increase in caloric ALK5 Inhibitor II intake toward the other extreme, particularly in North America. If there is a relationship between the redox state of the ETC, longevity, mtDNA mutations and extremes of caloric intake, it could be demonstrated by an analysis of historical longevity within mtDNA haplogroups during extended and continental periods of calorie reduction and over-consumption.