Clockwork Orangutan: microRNAs, thermoregulatory tradeoffs, and the evolution of brain size

SUMMARY Models of the expansion of brain size relative to body size in the human lineage have not accounted for thermal homeostasis. We demonstrate that mammalian brain and liver sizes vary inversely relative to a thermoregulatory Core (kidney+heart+liver+brain). Since the advent of placentation and permanent homeothermy depended on faster metabolic rates ( MR s) and coincided with increases in the number of microRNA families ( mirFam ), we rescaled MR /kg from log-based specific MR s to mirFam -based cellular MR s ( cMR s). Liver cMR varied inversely with respect to body mass and the cMR s of kidney, heart and brain, recapitulating the downregulation of gluconeogenesis during developmental growth of the liver and whole body. With mirFam as a proxy for energy reliability, a logistic feedback model of relative brain size detected adaptation to a low-energy regime among the smallest primates and, among the largest primates, adaptation to the physiological limit on the rate of heat dissipation.