Because secondary structure of the 5’ end of mRNA influences translational efficiency, synonymous changes at this region on the mRNA can result in profound effects on gene expression. Codon usage in noncoding DNA regions can therefore play a major role in RNA secondary structure and downstream protein expression, which can undergo further selective pressures. In particular, strong secondary structure at the ribosome-binding site or initiation codon can inhibit translation, and mRNA folding at the 5’ end generates a large amount of variation in protein levels.