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Essentiality is a strong determinant of protein rates of evolution during mutation accumulation experiments in Escherichia coli

Abstract:

TheNeutral Theory ofMolecular Evolution is considered themost powerful theory to understand the evolutionary behavior of proteins. One of the main pbkp_redictions of this theory is that essential proteins should evolve slower than dispensable ones owing to increased selective constraints. Comparison of genomes of different species, however, has revealed only small differences between the rates of evolution of essential and nonessential proteins. In someanalyses, these differences vanish once confounding factors are controlled for, whereas in other cases essentiality seems to have an independent, albeit small, effect. It has been argued that comparing relatively distant genomes may entail a number of limitations. For instance,many of the genes that are dispensable in controlled lab conditions may be essential in some of the conditions faced in nature. Moreover, essentiality can change during evolution, and rates of protein evolution are simultaneously shaped by a variety of factors, whose individual effects are difficult to isolate. Here, we conducted two parallel mutation accumulation experiments in Escherichia coli, during 5,500-5,750 generations, and compared the genomes at different pointsof theexperiments.Ourapproach (a short-Term experiment, underhighly controlled conditions) enabled us toovercome many of the limitations of previous studies. We observed that essential proteins evolved substantially slower than nonessential ones during our experiments. Strikingly, rates of protein evolution were only moderately affected by expression level and protein length.