Macroevolutionary divergence of gene expression driven by selection on protein abundance

The regulation of messenger RNA (mRNA) and protein abundances is well-studied, but less is known about the evolutionary processes shaping their relationship. To address this, we derived a new phylogenetic model and applied it to multispecies mammalian data. Our analyses reveal (i) strong stabilizing selection on protein abundances over macroevolutionary time, (ii) mutations affecting mRNA abundances minimally impact protein abundances, (iii) mRNA abundances evolve under selection to align with protein abundances, and (iv) mRNA abundances adapt faster than protein abundances owing to greater mutational opportunity. These conclusions are supported by comparisons of model parameters with independent functional genomic data. By decomposing mutational and selective influences on mRNA-protein dynamics, our approach provides a framework for discovering the evolutionary rules that drive divergence in gene expression.