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. Editor's summary: Proteins are translated from messenger RNA (mRNA), and the levels of these biomolecules are often correlated for a given gene. However, this observation is at odds with the fact that many variants that alter gene expression do not alter protein levels. Cope et al. tested several phylogenetic models relating mRNA and protein levels in coupled transcriptomic and proteomic data from skin samples across 10 mammals. They found that evolution primarily acting on protein levels best fit the data, with gene expression driven to accommodate those optimal levels. These mRNA values did not match perfectly and are likely amplified due to post-transcriptional mechanisms such as translational efficiency or protein degradation. —Corinne Simonti [ABSTRACT FROM AUTHOR]