RT Journal Article
SR Electronic
T1 Rapid Adaptation of Cellular Metabolic Rate to the microRNA Complements of Mammals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.24.517858
DO 10.1101/2022.11.24.517858
A1 Bastian Fromm
A1 Thomas Sorger
YR 2022
UL http://biorxiv.org/content/early/2022/11/25/2022.11.24.517858.abstract
AB Terrestrial 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 as sMR and 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. When sMR is fit to mirFam by maximum likelihood, the variation is homoscedastic, allowing us to compare models for the evolution of sMR in relation to mirFam. With mirFam as the predictor, an Ornstein-Uhlenbeck (OU) process of stabilizing selection accounted better for the biphasic evolution of sMR than did the corresponding Brownian motion model, and was optimized when sMR was scaled to M0.75. OU simulations with an adaptive shift at the divergence of Boreoeutheria predicted 95% of the variation in sMR. We infer that the advent of placentation led to the emergence of an adaptive optimum characterized by higher body temperatures, faster MRs, and heightened global microRNA activity.Competing Interest StatementThe authors have declared no competing interest.