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A model for protein sequence evolution based on selective pressure for protein stability: application to hemoglobins.

Marsh L - Evol. Bioinform. Online (2009)

Bottom Line: For diverse proteins the results were consistent with stability-based selection.Maximum likelihood studies with hemoglobins supported the stability-based model over simple Poisson-based methods.These observations are consistent with suggestions that purifying selection to maintain protein structural stability plays a dominant role in protein evolution.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Long Island University, Brooklyn, NY 11201, USA. lmarsh@liu.edu

ABSTRACT
Negative selection against protein instability is a central influence on evolution of proteins. Protein stability is maintained over evolution despite changes in underlying sequences. An empirical all-site stability-based model of evolution was developed to focus on the selection of residues arising from their contributions to protein stability. In this model, site rates could vary. A structure-based method was used to predict stationary frequencies of hemoglobin residues based on their propensity to promote protein stability at a site. Sites with destabilizing residues were shown to change more rapidly in hemoglobins than sites with stabilizing residues. For diverse proteins the results were consistent with stability-based selection. Maximum likelihood studies with hemoglobins supported the stability-based model over simple Poisson-based methods. These observations are consistent with suggestions that purifying selection to maintain protein structural stability plays a dominant role in protein evolution.

No MeSH data available.


Selection for stability in hemoglobins. Open circles, mean distribution of ΔΔG values of residues observed to occur in 9 hemoglobins (subject to selection); closed circles, mean distribution of ΔΔG values of all possible substitutions, estimated for 9 hemoglobins (unselected). ΔΔG estimated by Modeller-Fold-X analysis of protein structures.
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f1-ebo-2009-107: Selection for stability in hemoglobins. Open circles, mean distribution of ΔΔG values of residues observed to occur in 9 hemoglobins (subject to selection); closed circles, mean distribution of ΔΔG values of all possible substitutions, estimated for 9 hemoglobins (unselected). ΔΔG estimated by Modeller-Fold-X analysis of protein structures.

Mentions: Figure 1 shows the probability distribution of ΔΔG values for two sets of residues in 9 hemoglobins: all potential substitutions, and residues observed to occur in the proteins. The distribution of the stabilities for all possible substitutions (which included both residues that would permit folding and those which would not be compatible with folding) was relatively flat, consistent with the lack of selection for stability. The distribution of stabilities for observed residues on the other hand was roughly exponential with many values skewed toward very stable values. 30.8% of residues were in the most stable state (11.3% would be random) suggesting that stability represents a protein feature subject to selection for these hemoglobins. This result also suggested that error in stability estimation was low.


A model for protein sequence evolution based on selective pressure for protein stability: application to hemoglobins.

Marsh L - Evol. Bioinform. Online (2009)

Selection for stability in hemoglobins. Open circles, mean distribution of ΔΔG values of residues observed to occur in 9 hemoglobins (subject to selection); closed circles, mean distribution of ΔΔG values of all possible substitutions, estimated for 9 hemoglobins (unselected). ΔΔG estimated by Modeller-Fold-X analysis of protein structures.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2747123&req=5

f1-ebo-2009-107: Selection for stability in hemoglobins. Open circles, mean distribution of ΔΔG values of residues observed to occur in 9 hemoglobins (subject to selection); closed circles, mean distribution of ΔΔG values of all possible substitutions, estimated for 9 hemoglobins (unselected). ΔΔG estimated by Modeller-Fold-X analysis of protein structures.
Mentions: Figure 1 shows the probability distribution of ΔΔG values for two sets of residues in 9 hemoglobins: all potential substitutions, and residues observed to occur in the proteins. The distribution of the stabilities for all possible substitutions (which included both residues that would permit folding and those which would not be compatible with folding) was relatively flat, consistent with the lack of selection for stability. The distribution of stabilities for observed residues on the other hand was roughly exponential with many values skewed toward very stable values. 30.8% of residues were in the most stable state (11.3% would be random) suggesting that stability represents a protein feature subject to selection for these hemoglobins. This result also suggested that error in stability estimation was low.

Bottom Line: For diverse proteins the results were consistent with stability-based selection.Maximum likelihood studies with hemoglobins supported the stability-based model over simple Poisson-based methods.These observations are consistent with suggestions that purifying selection to maintain protein structural stability plays a dominant role in protein evolution.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Long Island University, Brooklyn, NY 11201, USA. lmarsh@liu.edu

ABSTRACT
Negative selection against protein instability is a central influence on evolution of proteins. Protein stability is maintained over evolution despite changes in underlying sequences. An empirical all-site stability-based model of evolution was developed to focus on the selection of residues arising from their contributions to protein stability. In this model, site rates could vary. A structure-based method was used to predict stationary frequencies of hemoglobin residues based on their propensity to promote protein stability at a site. Sites with destabilizing residues were shown to change more rapidly in hemoglobins than sites with stabilizing residues. For diverse proteins the results were consistent with stability-based selection. Maximum likelihood studies with hemoglobins supported the stability-based model over simple Poisson-based methods. These observations are consistent with suggestions that purifying selection to maintain protein structural stability plays a dominant role in protein evolution.

No MeSH data available.