Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover
Translational errors occur at high rates, and they influence organism viability and the onset of genetic diseases. 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 (mistra...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636289/ |
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pubmed-4636289 |
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pubmed-46362892015-11-13 Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover Kalapis, Dorottya Bezerra, Ana R. Farkas, Zoltán Horvath, Peter Bódi, Zoltán Daraba, Andreea Szamecz, Béla Gut, Ivo Bayes, Mónica Santos, Manuel A. S. Pál, Csaba Research Article Translational errors occur at high rates, and they influence organism viability and the onset of genetic diseases. 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). It thereby overloads the protein quality-control pathways and disrupts cellular protein homeostasis. This strain was used to study the capacity of the yeast genome to compensate the deleterious effects of protein mistranslation. Laboratory evolutionary experiments revealed that fitness loss due to mistranslation can rapidly be mitigated. 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. By altering the dosages of numerous, functionally related proteins simultaneously, these genetic changes introduced large phenotypic leaps that enabled rapid adaptation to mistranslation. Evolution increased the level of tolerance to mistranslation through acceleration of ubiquitin-proteasome–mediated protein degradation and protein synthesis. As a consequence of rapid elimination of erroneous protein products, evolution reduced the extent of toxic protein aggregation in mistranslating cells. 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. 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. We conclude that adjustment of proteome homeostasis to mistranslation evolves rapidly, but this adaptation has several side effects on cellular physiology. 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. Public Library of Science 2015-11-06 /pmc/articles/PMC4636289/ /pubmed/26544557 http://dx.doi.org/10.1371/journal.pbio.1002291 Text en © 2015 Kalapis et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Kalapis, Dorottya Bezerra, Ana R. Farkas, Zoltán Horvath, Peter Bódi, Zoltán Daraba, Andreea Szamecz, Béla Gut, Ivo Bayes, Mónica Santos, Manuel A. S. Pál, Csaba |
| spellingShingle |
Kalapis, Dorottya Bezerra, Ana R. Farkas, Zoltán Horvath, Peter Bódi, Zoltán Daraba, Andreea Szamecz, Béla Gut, Ivo Bayes, Mónica Santos, Manuel A. S. Pál, Csaba Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover |
| author_facet |
Kalapis, Dorottya Bezerra, Ana R. Farkas, Zoltán Horvath, Peter Bódi, Zoltán Daraba, Andreea Szamecz, Béla Gut, Ivo Bayes, Mónica Santos, Manuel A. S. Pál, Csaba |
| author_sort |
Kalapis, Dorottya |
| title |
Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover |
| title_short |
Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover |
| title_full |
Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover |
| title_fullStr |
Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover |
| title_full_unstemmed |
Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover |
| title_sort |
evolution of robustness to protein mistranslation by accelerated protein turnover |
| description |
Translational errors occur at high rates, and they influence organism viability and the onset of genetic diseases. 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). It thereby overloads the protein quality-control pathways and disrupts cellular protein homeostasis. This strain was used to study the capacity of the yeast genome to compensate the deleterious effects of protein mistranslation. Laboratory evolutionary experiments revealed that fitness loss due to mistranslation can rapidly be mitigated. 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. By altering the dosages of numerous, functionally related proteins simultaneously, these genetic changes introduced large phenotypic leaps that enabled rapid adaptation to mistranslation. Evolution increased the level of tolerance to mistranslation through acceleration of ubiquitin-proteasome–mediated protein degradation and protein synthesis. As a consequence of rapid elimination of erroneous protein products, evolution reduced the extent of toxic protein aggregation in mistranslating cells. 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. 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. We conclude that adjustment of proteome homeostasis to mistranslation evolves rapidly, but this adaptation has several side effects on cellular physiology. 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. |
| publisher |
Public Library of Science |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636289/ |
| _version_ |
1613498571888263168 |