Rapid Adaptation of Cellular Metabolic Rate to the microRNA Complements of Mammals

Abstract

ABSTRACTTerrestrial mammals range over six orders of magnitude in size, while average cellular, or specific metabolic rate(sMR) varies only ∼5-fold, constrained by the strict matching of protein synthesis to cell size. Protein synthesis, the single most costly metabolic activity, accounts for 20% of ATP turnover, and the speed of translation can be increased only at the expense of increased energy dissipation due to misreading errors and stochastic translation noise. We hypothesized that global microRNA activity evolved under the same constraints assMRand would therefore exhibit a similar pattern of variation. This expectation was met by the number of microRNA families: based on the manually curated microRNA gene database MirGeneDB, the acquisition of microRNA families (mirFam) accelerated two-fold in late-branching mammals with body temperatures (Tb) > 36°C, relative to early-branching mammals (Tb< 36°C), independent of phylogenetic distance. WhensMRis fit tomirFamby maximum likelihood, the variation is homoscedastic, allowing us to compare models for the evolution ofsMRin relation tomirFam. WithmirFamas the predictor, an Ornstein-Uhlenbeck (OU) process of stabilizing selection accounted better for the biphasic evolution ofsMRthan did the corresponding Brownian motion model, and was optimized whensMRwas scaled toM0.75. OU simulations with an adaptive shift at the divergence of Boreoeutheria predicted 95% of the variation insMR. We infer that the advent of placentation led to the emergence of an adaptive optimum characterized by higher body temperatures, fasterMRs, and heightened global microRNA activity.