Phylogenetic analysis reveals how selection and mutation shape the coevolution of mRNA and protein abundances

The regulatory mechanisms that shape mRNA and protein abundances are intensely studied. Much less is known about the evolutionary processes that shape the relationship between these two levels of gene expression. To disentangle the contributions of mutational and selective processes, we derive a novel phylogenetic model and fit it to multi-species data from mammalian skin tissue. We find that over macroevolutionary time: 1) there has been strong stabilizing selection on protein abundances; 2) mutations impacting mRNA abundances have minimal influence on protein abundances; 3) mRNA abundances are under selection to track protein abundances, and 4) mRNA abundances adapt more quickly than protein abundances due to increased mutational opportunity. We find additional support for these findings by comparing gene-specific parameter estimates from our model to human functional genomic data. More broadly, our new phylogenetic approach provides a foundation for testing hypotheses about the processes that led to divergence in gene expression.