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Highly expressed and slowly evolving proteins share compositional properties with thermophilic proteins.

Cherry JL - Mol. Biol. Evol. (2009)

Bottom Line: Proteins from thermophiles generally have more stable folds than proteins from mesophiles, and it is known that there are systematic differences in amino acid content between thermophilic and mesophilic proteins.These results suggest that part of the evolutionary rate variation among proteins is due to variation in the strength of selection for stability of the folded state.They also suggest that increasing strength of this selective force with expression level plays a role in the correlation between evolutionary rate and expression level.

View Article: PubMed Central - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. jcherry@ncbi.nlm.nih.gov

ABSTRACT
The sequences of proteins encoded by a genome evolve at different rates. A correlate of a protein's evolutionary rate is its expression level: highly expressed proteins tend to evolve slowly. Some explanations of rate variation and the correlation between rate and expression predict that more slowly evolving and more highly expressed proteins have more favorable equilibrium constants for folding. Proteins from thermophiles generally have more stable folds than proteins from mesophiles, and it is known that there are systematic differences in amino acid content between thermophilic and mesophilic proteins. I examined whether there are analogous correlations of amino acid frequencies with evolutionary rate and expression level within genomes. In most of the organisms analyzed, there is a striking tendency for more slowly evolving proteins to be more thermophile-like in their amino acid compositions when adjustments are made for variation in GC content. More highly expressed proteins also tend to be more thermophile-like by the same criteria. These results suggest that part of the evolutionary rate variation among proteins is due to variation in the strength of selection for stability of the folded state. They also suggest that increasing strength of this selective force with expression level plays a role in the correlation between evolutionary rate and expression level.

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Summary of correlation results for dN across organisms. For each correlation, “+” indicates a statistically significant (P < 0.05) positive correlation, “−” indicates a significant negative correlation, and “ns” indicates that the correlation was not statistically significant. Negative correlations, which are predicted for amino acids more common are thermophiles, are also indicated by orange coloring, and positive correlations are indicated by blue coloring.
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fig2: Summary of correlation results for dN across organisms. For each correlation, “+” indicates a statistically significant (P < 0.05) positive correlation, “−” indicates a significant negative correlation, and “ns” indicates that the correlation was not statistically significant. Negative correlations, which are predicted for amino acids more common are thermophiles, are also indicated by orange coloring, and positive correlations are indicated by blue coloring.

Mentions: The correlations of dN with each amino acid frequency are summarized graphically in figure 2. The abundance of negative correlations for amino acids that are more frequent in thermophilic proteins, and positive correlations for amino acids with the opposite tendency, is apparent. Neglecting C. briggsae (but including the C. briggsae dS < 1 results), the only amino acids whose frequencies ever correlate significantly in the “wrong” direction are alanine (A) and tryptophan (W), the latter of which had no significant correlation with optimal growth temperature according to Zeldovich et al. (2007). Despite being discordant in some organisms, both A and W correlate in the expected direction in other organisms. For each of the other nine amino acids in SH-11, there is a consensus of sorts: all of the significant correlations have the same sign, and there is more than one significant correlation. In all nine cases in which there is a consensus, the consensus is in accord with the hypothesis that more slowly evolving proteins are more like thermophilic proteins.


Highly expressed and slowly evolving proteins share compositional properties with thermophilic proteins.

Cherry JL - Mol. Biol. Evol. (2009)

Summary of correlation results for dN across organisms. For each correlation, “+” indicates a statistically significant (P < 0.05) positive correlation, “−” indicates a significant negative correlation, and “ns” indicates that the correlation was not statistically significant. Negative correlations, which are predicted for amino acids more common are thermophiles, are also indicated by orange coloring, and positive correlations are indicated by blue coloring.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2822289&req=5

fig2: Summary of correlation results for dN across organisms. For each correlation, “+” indicates a statistically significant (P < 0.05) positive correlation, “−” indicates a significant negative correlation, and “ns” indicates that the correlation was not statistically significant. Negative correlations, which are predicted for amino acids more common are thermophiles, are also indicated by orange coloring, and positive correlations are indicated by blue coloring.
Mentions: The correlations of dN with each amino acid frequency are summarized graphically in figure 2. The abundance of negative correlations for amino acids that are more frequent in thermophilic proteins, and positive correlations for amino acids with the opposite tendency, is apparent. Neglecting C. briggsae (but including the C. briggsae dS < 1 results), the only amino acids whose frequencies ever correlate significantly in the “wrong” direction are alanine (A) and tryptophan (W), the latter of which had no significant correlation with optimal growth temperature according to Zeldovich et al. (2007). Despite being discordant in some organisms, both A and W correlate in the expected direction in other organisms. For each of the other nine amino acids in SH-11, there is a consensus of sorts: all of the significant correlations have the same sign, and there is more than one significant correlation. In all nine cases in which there is a consensus, the consensus is in accord with the hypothesis that more slowly evolving proteins are more like thermophilic proteins.

Bottom Line: Proteins from thermophiles generally have more stable folds than proteins from mesophiles, and it is known that there are systematic differences in amino acid content between thermophilic and mesophilic proteins.These results suggest that part of the evolutionary rate variation among proteins is due to variation in the strength of selection for stability of the folded state.They also suggest that increasing strength of this selective force with expression level plays a role in the correlation between evolutionary rate and expression level.

View Article: PubMed Central - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. jcherry@ncbi.nlm.nih.gov

ABSTRACT
The sequences of proteins encoded by a genome evolve at different rates. A correlate of a protein's evolutionary rate is its expression level: highly expressed proteins tend to evolve slowly. Some explanations of rate variation and the correlation between rate and expression predict that more slowly evolving and more highly expressed proteins have more favorable equilibrium constants for folding. Proteins from thermophiles generally have more stable folds than proteins from mesophiles, and it is known that there are systematic differences in amino acid content between thermophilic and mesophilic proteins. I examined whether there are analogous correlations of amino acid frequencies with evolutionary rate and expression level within genomes. In most of the organisms analyzed, there is a striking tendency for more slowly evolving proteins to be more thermophile-like in their amino acid compositions when adjustments are made for variation in GC content. More highly expressed proteins also tend to be more thermophile-like by the same criteria. These results suggest that part of the evolutionary rate variation among proteins is due to variation in the strength of selection for stability of the folded state. They also suggest that increasing strength of this selective force with expression level plays a role in the correlation between evolutionary rate and expression level.

Show MeSH