Solvent exposure imparts similar selective pressures across a range of yeast proteins.

We study how an amino acid residue's solvent exposure influences its propensity for substitution by analyzing multiple alignments of 61 yeast genes for which the crystal structure is known. We find that the selective constraint on the interior residues is on average 10 times that of residues on the surface. Surprisingly, there is no correlation between the overall selective constraint observed for a protein alignment and the ratio of constraints on interior and surface residues. By modeling the selective constraint on several amino acid properties, we show that although residue volume and hydropathy are strongly conserved across most alignments, there is little variation in interior versus surface conservation for these two properties. By contrast, residue charge (isoelectric point) is less generally conserved when considering the protein as a whole but shows a strong constraint against the introduction of charged residues into the protein interior.