Slow protein evolutionary rates are dictated by surface-core association

Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11151-6. doi: 10.1073/pnas.1015994108. Epub 2011 Jun 20.

Abstract

Why do certain proteins evolve much slower than others? We compared not only rates per protein, but also rates per position within individual proteins. For ∼90% of proteins, the distribution of positional rates exhibits three peaks: a peak of slow evolving residues, with average log(2)[normalized rate], log(2)μ, of ca. -2, corresponding primarily to core residues; a peak of fast evolving residues (log(2)μ ∼ 0.5) largely corresponding to surface residues; and a very fast peak (log(2)μ ∼ 2) associated with disordered segments. However, a unique fraction of proteins that evolve very slowly exhibit not only a negligible fast peak, but also a peak with a log(2)μ ∼ -4, rather than the standard core peak of -2. Thus, a "freeze" of a protein's surface seems to stop core evolution as well. We also observed a much higher fraction of substitutions in potentially interacting residues than expected by chance, including substitutions in pairs of contacting surface-core residues. Overall, the data suggest that accumulation of surface substitutions enables the acceptance of substitutions in core positions. The underlying reason for slow evolution might therefore be a highly constrained surface due to protein-protein interactions or the need to prevent misfolding or aggregation. If the surface is inaccessible to substitutions, so becomes the core, thus resulting in very slow overall rates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida glabrata / chemistry
  • Candida glabrata / genetics
  • Databases, Protein
  • Evolution, Molecular*
  • Fungal Proteins / chemistry*
  • Fungal Proteins / genetics*
  • Kluyveromyces / chemistry
  • Kluyveromyces / genetics
  • Models, Molecular
  • Mutation
  • Phylogeny
  • Protein Stability
  • Protein Structure, Tertiary
  • Saccharomyces / chemistry
  • Saccharomyces / genetics
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Structural Homology, Protein
  • Time Factors
  • Yeasts / chemistry
  • Yeasts / classification
  • Yeasts / genetics

Substances

  • Fungal Proteins
  • Saccharomyces cerevisiae Proteins