Why proteins evolve at different rates: The functional hypothesis versus the mistranslation-induced protein misfolding hypothesis

Abstract 

Protein evolutionary rates have been presumed to be mostly determined by the density of functionally important amino acids in a given protein. They have been shown to correlate with variables intuitively related to functional importance of proteins, such as protein dispensability and protein–protein interactions. Surprisingly, the best correlate of the evolutionary rates has turned out to be not the functional importance of a protein, but the expression level of the protein. Drummond and Wilke suggest that the dominant role of expression levels in slowing the rate of protein evolution stems from a selection pressure against mistranslation-induced protein misfolding. We will review current evidence for and against different hypotheses on determining evolutionary rates.

Keywords: Protein evolutionary rate, Functional hypothesis, Mistranslation-induced protein misfolding hypothesis, Translational robustness, Expression abundance