Proportion of Solvent-Exposed Amino Acids in a Protein and Rate of Protein Evolution

• Three major proposed hypotheses explaining large variation of protein evolutionary rate:
  • Functionally less important proteins evolve faster than more important ones
  • Functional density: Rate determined by the proportion of residues involved in specific functions
  • Translational selection: the number of translation events a gene experiences determines its evolutionary rate

• Dickerson (1971): surface residues that interact with other proteins tend to be highly conserved
• Solvent inaccessible core of a protein better conserved than the solvent accessible residues
• Residues in the core and exposed residues shown to have different substitution patterns due to different selection pressures (Tseng and Liang 2006)

• Problems with PDB data: Failed to parse (Cannot write to or create math temp directory): P_{exposed}

is not known but must be estimated

• Structurally less well-determined proteins usually contain disordered regions, which have mainly exposed residues and have been found to evolve rapidly (Brown 1992)

• Because disordered regions not determined in 3D structure and are usually solvent exposed, Failed to parse (Cannot write to or create math temp directory): P_{exposed}

is likely to increase with the disordered regions

• Results suggest that disordered regions in a protein may largely determine its Failed to parse (Cannot write to or create math temp directory): P_{exposed}

and evolutionary rate

• For proteins with fewer disordered residues, Failed to parse (Cannot write to or create math temp directory): P_{exposed}

is negatively correlated with evolutionary rate 

• Proteins with a high Failed to parse (Cannot write to or create math temp directory): P_{exposed}

may evolve slowly or fast but a low Failed to parse (Cannot write to or create math temp directory): P_{exposed}
almost always has a low evolutionary rate

• Thus, 3D structure might provide only a general index--buried residues cannot evolve freely, but some exposed residues are functionally important and thus conserved

• Increasing a proteins thermodynamic ability increases its tolerance to mutations--might mean deleterious mutations usually act by hindering the formation of a properly folded protein rather than altering a protein's function

• Likely that buried residues are conserved because they are important to make proteins fold or interact correctly among subunits or proteins

• A protein with more residues under selective constraint tends to evolve more slowly