The rate of the molecular clock and the cost ofgratuitous protein synthesis

摘要

Background: The nature of the protein molecular clock, the protein-specific rate of amino acid substitutions, isamong the central questions of molecular evolution. Protein expression level is the dominant determinant of theclock rate in a number of organisms. It has been suggested that highly expressed proteins evolve slowly in allspecies mainly to maintain robustness to translation errors that generate toxic misfolded proteins. Here weinvestigate this hypothesis experimentally by comparing the growth rate of Escherichia coli expressing wild typeand misfolding-prone variants of the LacZ protein. Results: We show that the cost of toxic protein misfolding is small compared to other costs associated withprotein synthesis. Complementary computational analyses demonstrate that there is also a relatively weaker, butstatistically significant, selection for increasing solubility and polarity in highly expressed E. coli proteins. Conclusions: Although we cannot rule out the possibility that selection against misfolding toxicity significantlyaffects the protein clock in species other than E. coli, our results suggest that it is unlikely to be the dominant anduniversal factor determining the clock rate in all organisms. We find that in this bacterium other costs associatedwith protein synthesis are likely to play an important role. Interestingly, our experiments also suggest significantcosts associated with volume effects, such as jamming of the cellular environment with unnecessary proteins.