Genomic and Environmental Selection on Local mRNA Folding Strength in Protein-coding Sequences Across the Tree of Life

Local mRNA folding strength can be increased or decreased at different regions of the transcript through the choice of synonymous codons. This modulation of local folding strength is thought to affect many aspects of gene expression: it changes the translation initiation rate and the local rate of translation elongation, alters co-translational protein folding, prevents aggregation of mRNA molecules, and can even influence the transcription rate.

In this study we analyze local mRNA folding strengths in genomes across the tree of life to see how they interact with genomic and environmental traits, in order to shed light on the mechanisms involved in maintaining them. We show that local folding strength follows a characteristic profile that is conserved in most bacterial and archaeal species (but not in eukaryotes). The relation between local folding strength and genomic GC-content follows universal and taxon-specific trends. Interactions with environmental traits provide additional evidence for selection maintaining local folding strength.

These results should advance the understanding of mRNA secondary structure in native proteins, and thus promote developing novel engineering approaches for controlling gene expression in non-model organisms.