Biophysical constraints on mRNA decay rates shape macroevolutionary divergence in steady-state abundances

Evolutionary changes to gene expression are understood to be a major driver of phenotypic divergence between species. Researchers have investigated the drivers of this divergence by fitting evolutionary models to multi-species ‘omic’ datasets. It is now apparent that steady-state mRNA expression levels show patterns consistent with evolutionary constraints, likely as a consequence of stabilizing selection. However, as all previous work has used bulk RNA measurements, it has been impossible to determine which of the many cellular processes that contribute to steady-state abundances underlie the divergence between species. Here we develop a novel paradigm for addressing this open problem. Using multi-species single-cell expression data and biophysical models, we estimate mRNA transcriptional burst sizes, splicing rates and decay rates across multiple species. We then derive phylogenetic models that describe the divergence of these rates under alternative evolutionary scenarios and fit these to the comparative data. We find evidence for biophysical constraints on the rates of mRNA decay, such that macroevolutionary divergence in expression is primarily a consequence of variation in transcriptional bursting.