A Model for Protein Sequence Evolution Based on Selective Pressure for Protein Stability: Application to Hemoglobins
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...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2009-01-01
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| Series: | Evolutionary Bioinformatics |
| Online Access: | https://doi.org/10.4137/EBO.S3120 |
| Summary: | 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. |
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| ISSN: | 1176-9343 |