Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover

Dorottya Kalapis, Ana R. Bezerra, Zoltán Farkas, Peter Horvath, Zoltán Bódi, Andreea Daraba, Béla Szamecz, Ivo Gut, Mónica Bayes, Manuel A S Santos, C. Pál

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere1002291
JournalPLoS Biology
Volume13
Issue number11
DOIs
Publication statusPublished - Nov 6 2015

Fingerprint

protein metabolism
protein synthesis
ubiquitin
Proteins
proteins
homeostasis
yeasts
genome
protein products
organisms
proteasome endopeptidase complex
genetic disorders
hexoses
Genes
Ubiquitin
protein degradation
proteome
ribosomes
codons
quality control

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Kalapis, D., Bezerra, A. R., Farkas, Z., Horvath, P., Bódi, Z., Daraba, A., ... Pál, C. (2015). Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover. PLoS Biology, 13(11), [e1002291]. https://doi.org/10.1371/journal.pbio.1002291

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, C.

In: PLoS Biology, Vol. 13, No. 11, e1002291, 06.11.2015.

Research output: Contribution to journalArticle

Kalapis, D, Bezerra, AR, Farkas, Z, Horvath, P, Bódi, Z, Daraba, A, Szamecz, B, Gut, I, Bayes, M, Santos, MAS & Pál, C 2015, 'Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover', PLoS Biology, vol. 13, no. 11, e1002291. https://doi.org/10.1371/journal.pbio.1002291
Kalapis D, Bezerra AR, Farkas Z, Horvath P, Bódi Z, Daraba A et al. Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover. PLoS Biology. 2015 Nov 6;13(11). e1002291. https://doi.org/10.1371/journal.pbio.1002291
Kalapis, Dorottya ; Bezerra, Ana R. ; Farkas, Zoltán ; Horvath, Peter ; Bódi, Zoltán ; Daraba, Andreea ; Szamecz, Béla ; Gut, Ivo ; Bayes, Mónica ; Santos, Manuel A S ; Pál, C. / Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover. In: PLoS Biology. 2015 ; Vol. 13, No. 11.
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