A Model for Protein Sequence Evolution Based on Selective Pressure for Protein Stability: Application to Hemoglobins

• Main Author: Lorraine Marsh
• Format: Article
• Language: English
• Published: SAGE Publishing 2009-01-01
• Series: Evolutionary Bioinformatics
• Online Access: https://doi.org/10.4137/EBO.S3120

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.