![]() ![]() This strain was used to study the capacity of the yeast genome to compensate for the deleterious effects of protein mistranslation. This thereby overloads the protein quality-control pathways and disrupts cellular protein homeostasis. A mutant yeast strain was engineered to translate a codon ambiguously (mistranslation). In this paper, for the first time, we study organisms’ capacity to evolve robustness against mistranslation and explore the underlying cellular mechanisms. These considerations raise the question as to how organisms can tolerate errors during protein synthesis. Such errors during protein synthesis can have a substantial influence on viability and the onset of genetic diseases. Our work also indicates that translational fidelity and the ubiquitin-proteasome system are functionally linked to each other and may, therefore, co-evolve in nature.Īlthough fidelity of information transfer has a substantial impact on cellular survival, many steps in protein production are strikingly error-prone. We conclude that adjustment of proteome homeostasis to mistranslation evolves rapidly, but this adaptation has several side effects on cellular physiology. Moreover, as a response to an enhanced energy demand of accelerated protein turnover, the evolved lines exhibited increased glucose uptake by selective duplication of hexose transporter genes. However, there was a strong evolutionary trade-off between adaptation to mistranslation and survival upon starvation: the evolved lines showed fitness defects and impaired capacity to degrade mature ribosomes upon nutrient limitation. As a consequence of rapid elimination of erroneous protein products, evolution reduced the extent of toxic protein aggregation in mistranslating cells. Evolution increased the level of tolerance to mistranslation through acceleration of ubiquitin-proteasome–mediated protein degradation and protein synthesis. By altering the dosages of numerous, functionally related proteins simultaneously, these genetic changes introduced large phenotypic leaps that enabled rapid adaptation to mistranslation. Genomic analysis demonstrated that adaptation was primarily mediated by large-scale chromosomal duplication and deletion events, suggesting that errors during protein synthesis promote the evolution of genome architecture. Laboratory evolutionary experiments revealed that fitness loss due to mistranslation can rapidly be mitigated. This strain was used to study the capacity of the yeast genome to compensate the deleterious effects of protein mistranslation. It thereby overloads the protein quality-control pathways and disrupts cellular protein homeostasis. To investigate how organisms mitigate the deleterious effects of protein synthesis errors during evolution, a mutant yeast strain was engineered to translate a codon ambiguously (mistranslation). Translational errors occur at high rates, and they influence organism viability and the onset of genetic diseases. ![]()
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