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Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover.

Kalapis D, Bezerra AR, Farkas Z, Horvath P, Bódi Z, Daraba A, Szamecz B, Gut I, Bayes M, Santos MA, Pál C - PLoS Biol. (2015)

Bottom Line: As a consequence of rapid elimination of erroneous protein products, evolution reduced the extent of toxic protein aggregation in mistranslating cells.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.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.

View Article: PubMed Central - PubMed

Affiliation: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.

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.

No MeSH data available.


Related in: MedlinePlus

Gene expression changes as a function of copy number variation.The figure shows mRNA expression fold change in evolved line 1 relative to the corresponding ancestor. As expected, loss of a small part of one copy of chromosome V (deletion) leads to reduced mRNA levels of the corresponding genes, while the opposite is true for genes carried on duplicated segments of VII (Dup1), IX (Dup2) and XIII (Dup3). Center lines show mean ± 95% confidence interval. Fold change differences across the three main categories (duplication, deletion, and no change) are highly significant (t test, p < 10−6 for each comparison).
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pbio.1002291.g002: Gene expression changes as a function of copy number variation.The figure shows mRNA expression fold change in evolved line 1 relative to the corresponding ancestor. As expected, loss of a small part of one copy of chromosome V (deletion) leads to reduced mRNA levels of the corresponding genes, while the opposite is true for genes carried on duplicated segments of VII (Dup1), IX (Dup2) and XIII (Dup3). Center lines show mean ± 95% confidence interval. Fold change differences across the three main categories (duplication, deletion, and no change) are highly significant (t test, p < 10−6 for each comparison).

Mentions: Last, we studied the impact of the accumulated mutations on genomic expression. The analysis focused on two independently evolved strains (lines 1 and 4), both of which carried typical large-scale genomic rearrangements (Table 1). We grew these strains to mid-log phase in standard laboratory medium and measured genomic expression relative to the ancestor strain (DNA microarrays were used for this purpose). Only genes that showed at least a 2-fold change in expression were considered further. As expected, copy number variation had a significant impact on gene expression in the evolved lines (Fig 2, see S3 Table for the full dataset).


Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover.

Kalapis D, Bezerra AR, Farkas Z, Horvath P, Bódi Z, Daraba A, Szamecz B, Gut I, Bayes M, Santos MA, Pál C - PLoS Biol. (2015)

Gene expression changes as a function of copy number variation.The figure shows mRNA expression fold change in evolved line 1 relative to the corresponding ancestor. As expected, loss of a small part of one copy of chromosome V (deletion) leads to reduced mRNA levels of the corresponding genes, while the opposite is true for genes carried on duplicated segments of VII (Dup1), IX (Dup2) and XIII (Dup3). Center lines show mean ± 95% confidence interval. Fold change differences across the three main categories (duplication, deletion, and no change) are highly significant (t test, p < 10−6 for each comparison).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4636289&req=5

pbio.1002291.g002: Gene expression changes as a function of copy number variation.The figure shows mRNA expression fold change in evolved line 1 relative to the corresponding ancestor. As expected, loss of a small part of one copy of chromosome V (deletion) leads to reduced mRNA levels of the corresponding genes, while the opposite is true for genes carried on duplicated segments of VII (Dup1), IX (Dup2) and XIII (Dup3). Center lines show mean ± 95% confidence interval. Fold change differences across the three main categories (duplication, deletion, and no change) are highly significant (t test, p < 10−6 for each comparison).
Mentions: Last, we studied the impact of the accumulated mutations on genomic expression. The analysis focused on two independently evolved strains (lines 1 and 4), both of which carried typical large-scale genomic rearrangements (Table 1). We grew these strains to mid-log phase in standard laboratory medium and measured genomic expression relative to the ancestor strain (DNA microarrays were used for this purpose). Only genes that showed at least a 2-fold change in expression were considered further. As expected, copy number variation had a significant impact on gene expression in the evolved lines (Fig 2, see S3 Table for the full dataset).

Bottom Line: As a consequence of rapid elimination of erroneous protein products, evolution reduced the extent of toxic protein aggregation in mistranslating cells.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.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.

View Article: PubMed Central - PubMed

Affiliation: Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.

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.

No MeSH data available.


Related in: MedlinePlus