Quantitative Residue-Level Structure–Evolution Relationships in the Yeast Membrane Proteome

Bioinformatics Program, Department of Chemistry, Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Genome Biology and Evolution (Impact Factor: 4.23). 03/2013; 5(4). DOI: 10.1093/gbe/evt039
Source: PubMed


Membrane proteins exist in distinctly different environments from soluble proteins, resulting in differences between their respective biophysical and evolutionary properties. In comparison with soluble proteins, relatively little is known about how the unique biophysical properties of membrane proteins affect their evolutionary properties at the residue level. In particular, transmembrane regions of membrane proteins tend to be more conserved than regions outside of the membrane (extramembrane regions), but the mechanisms underlying this phenomenon are not well-understood. Here, we combine homology-based high-resolution three-dimensional protein models with rigorous evolutionary rate calculations to quantitatively assess residue-level structure-evolution relationships in the yeast membrane proteome. We find that residue evolutionary rate increases linearly with decreasing residue burial, regardless of the hydrophobic or hydrophilic nature of the solvent environment. This finding supports a direct relationship between a residue's selective constraint and the extent of its packing interactions with neighboring residues, independent of hydrophobic effects. Most importantly, for a fixed degree of burial, residues from transmembrane regions tend to evolve more slowly than residues from extramembrane regions. We attribute this difference to the increased importance of packing constraints and the decreased importance of hydrophobic effects in transmembrane regions. This additional selective constraint on transmembrane residues plays a dominant role in explaining why transmembrane regions evolve more slowly than extramembrane regions. In addition to revealing the universality of the linear relationship between residue burial and selective constraint across solvent environments, our work highlights the distinct residue-level evolutionary consequences imposed by the unique biophysical properties of the membrane environment.

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