title: Slow protein evolutionary rates are dictated by surface-core association.
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.
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Agnes
authors.initials: A
authors.lastname: Tóth-Petróczy
authors.forename: Dan S
authors.initials: DS
authors.lastname: Tawfik
mesh_terms: D041221:Candida glabrata / Q000737:chemistry / Q000235:genetics; D030562:Databases, Protein; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics*; D007716:Kluyveromyces / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D009154:Mutation; D010802:Phylogeny; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D012440:Saccharomyces / Q000737:chemistry / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics; D040681:Structural Homology, Protein; D013997:Time Factors; D015003:Yeasts / Q000737:chemistry / Q000145:classification / Q000235:genetics
chemical_list: D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins