Abstract
Phenotypic mutations are amino acid changes caused by mistranslation. How phenotypic mutations affect the adaptive evolution of new protein functions is unknown. Here we evolve the antibiotic resistance protein TEM-1 towards resistance on the antibiotic cefotaxime in an Escherichia coli strain with a high mistranslation rate. TEM-1 populations evolved in such strains endow host cells with a general growth advantage, not only on cefotaxime but also on several other antibiotics that ancestral TEM-1 had been unable to deactivate. High-throughput sequencing of TEM-1 populations shows that this advantage is associated with a lower incidence of weakly deleterious genotypic mutations. Our observations show that mistranslation is not just a source of noise that delays adaptive evolution. It could even facilitate adaptive evolution by exacerbating the effects of deleterious mutations and leading to their more efficient purging. The ubiquity of mistranslation and its effects render mistranslation an important factor in adaptive protein evolution.
Highlights
Phenotypic mutations are amino acid changes caused by mistranslation
To study how protein mistranslation might affect the evolution of a new protein function, we performed laboratory evolution experiments on the antibiotic resistance enzyme TEM-1 b-lactamase
The first is that strongly beneficial genotypic mutations sweep through both error-prone and wild-type E. coli populations, but the number of such sweeps is consistently smaller in error-prone strains (Supplementary Fig. 3a, Supplementary Discussion)
Summary
Phenotypic mutations are amino acid changes caused by mistranslation. How phenotypic mutations affect the adaptive evolution of new protein functions is unknown. Mistranslation could accelerate adaptive evolution, because a beneficial phenotypic mutation can create a high fitness protein from a low fitness genotypic intermediate[9]. Even few high-fitness proteins may ensure a population’s survival and buy the population enough time until genetic mutations make the adaptive change permanent[9,21,22]. It is unknown whether such ‘stepping stone’ proteins exist in the evolution of new protein functions by amino acid-changing mutations, they may have been involved in the evolution of new protein localization signals via read-through mutations[23,24]. This advantage is associated with increased purging of deleterious mutations, which can increase mean population fitness
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