Rapid adaptation of cellular metabolic rate to the MicroRNA complements of mammals and its relevance to the evolution of endothermy.

The metabolic efficiency of mammalian cells depends on the attenuation of intrinsic translation noise by microRNAs. We devised a metric of cellular metabolic rate (, / optimally fit to the number of microRNA families (), that is robust to variation in mass and sensitive to body temperature (), consistent with the heat dissipation limit theory of Speakman and Król (2010). Using as predictor, an Ornstein-Uhlenbeck process of stabilizing selection, with an adaptive shift at the divergence of Boreoeutheria, accounted for 95% of the variation in across mammals. Branchwise rates of evolution of , and concurrently increased 6- to 7-fold at the divergence of Boreoeutheria, independent of mass. Cellular variation across placental mammals was also predicted by the sum of model conserved microRNA-target interactions, revealing an unexpected degree of integration of the microRNA-target apparatus into the energy economy of the mammalian cell.