Correlation between protein abundance and sequence conservation: what do recent experiments say?

Bédard, Camille; Cisneros, Angel F.; Jordan, David Starr; Landry, Christian R.

doi:10.1016/j.gde.2022.101984

Cited by 10 publications

(11 citation statements)

References 42 publications

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“…One hypothesis to explain why mt aaRS sequences evolve rapidly in animals is that they are expressed at the lower levels than cytosolic aaRSs ( Adrion et al 2016 ; Barreto et al 2018 ), and expression tends to be negatively correlated with rates of protein evolution—the so-called E–R anticorrelation ( Zhang and Yang 2015 ; Bédard et al 2022 ). Indeed, mRNA transcript abundance for mt aaRS has been shown to be approximately 5-fold lower than for cytosolic aaRSs in multiple animal systems ( Adrion et al 2016 ).…”

Section: Resultsmentioning

confidence: 99%

Aminoacyl-tRNA Synthetase Evolution within the Dynamic Tripartite Translation System of Plant Cells

Sloan

DeTar

Warren

2023

Genome Biology and Evolution

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Eukaryotes maintain separate protein translation systems for nuclear and organellar genes, including distinct sets of tRNAs and aminoacyl-tRNA synthetases (aaRSs). In animals, mitochondrial-targeted aaRSs are expressed at lower levels and are less conserved in sequence than cytosolic aaRSs involved in translation of nuclear mRNAs, likely reflecting lower translational demands in mitochondria. In plants, translation is further complicated by the presence of plastids, which share most aaRSs with mitochondria. In addition, plant mitochondrial tRNA pools have a dynamic history of gene loss and functional replacement by tRNAs from other compartments. To investigate the consequences of these distinctive features of translation in plants, we analyzed sequence evolution in angiosperm aaRSs. In contrast to previously studied eukaryotic systems, we found that plant organellar and cytosolic aaRSs exhibit only a small difference in expression levels, and organellar aaRSs are slightly more conserved than cytosolic aaRSs. We hypothesize that these patterns result from high translational demands associated with photosynthesis in mature chloroplasts. We also investigated aaRS evolution in Sileneae, an angiosperm lineage with extensive mitochondrial tRNA replacement and aaRS retargeting. We predicted positive selection for changes in aaRS sequence resulting from these recent changes in subcellular localization and tRNA substrates but found little evidence for accelerated sequence divergence. Overall, the complex tripartite translation system in plant cells appears to have imposed more constraints on the long-term evolutionary rates of organellar aaRSs compared to other eukaryotic lineages, and plant aaRS protein sequences appear largely robust to more recent perturbations in subcellular localization and tRNA interactions.

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Section: Resultsmentioning

confidence: 99%

Aminoacyl-tRNA Synthetase Evolution within the Dynamic Tripartite Translation System of Plant Cells

Sloan

DeTar

Warren

2023

Genome Biology and Evolution

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“…S5). Similarly, computational estimations of mutational effects generally have a good agreement with experimental values but are not always as accurate ( 31 , 32 ). FoldX assumes a rigid backbone, which restricts the study of misfolding induced by mutations ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Epistasis between promoter activity and coding mutations shapes gene evolvability

et al. 2023

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The evolution of protein-coding genes proceeds as mutations act on two main dimensions: regulation of transcription level and the coding sequence. The extent and impact of the connection between these two dimensions are largely unknown because they have generally been studied independently. By measuring the fitness effects of all possible mutations on a protein complex at various levels of promoter activity, we show that promoter activity at the optimal level for the wild-type protein masks the effects of both deleterious and beneficial coding mutations. Mutations that are deleterious at low activity but masked at optimal activity are slightly destabilizing for individual subunits and binding interfaces. Coding mutations that increase protein abundance are beneficial at low expression but could potentially incur a cost at high promoter activity. We thereby demonstrate that promoter activity in interaction with protein properties can dictate which coding mutations are beneficial, neutral, or deleterious.

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“…Although focusing on one particular protein, our results may shed light on a long-standing observation in molecular evolution. Highly expressed proteins evolve slowly ( 35 , 36 ) and this is often interpreted as higher selective constraints acting on highly expressed proteins, for instance to prevent misfolding and potentially misinteraction, which would be costly. We found potential misfolding to have no detectable effects for this protein, which could be the case for many other proteins as well.…”

Section: Discussionmentioning

confidence: 99%

Epistasis between promoter activity and coding mutations shapes gene evolvability

Cisneros

Gagnon‐Arsenault

Dubé

et al. 2022

Preprint

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The evolution of protein-coding genes proceeds as mutations act on two main dimensions: regulation of transcription level and the coding sequence. The extent and impact of the connection between these two dimensions are largely unknown because they have generally been studied independently. By measuring the fitness effects of all possible mutations on a protein complex at various levels of promoter activity, we show that expression at the optimal level for the WT protein masks the effects of both deleterious and beneficial coding mutations. Mutants that are deleterious at low expression but masked at optimal expression are slightly destabilizing for individual subunits and binding interfaces. Coding mutations that increase protein abundance are beneficial at low expression but incur a fitness cost at high expression. We thereby demonstrate that expression level can dictate which coding mutations are beneficial or deleterious.

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Correlation between protein abundance and sequence conservation: what do recent experiments say?

Cited by 10 publications

References 42 publications

Aminoacyl-tRNA Synthetase Evolution within the Dynamic Tripartite Translation System of Plant Cells

Aminoacyl-tRNA Synthetase Evolution within the Dynamic Tripartite Translation System of Plant Cells

Epistasis between promoter activity and coding mutations shapes gene evolvability

Epistasis between promoter activity and coding mutations shapes gene evolvability

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