Signatures of protein biophysics in coding sequence evolution
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Updated: Jun 13, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Claus O Wilke1, D Allan Drummond
1Center for Computational Biology and Bioinformatics, Institute for Cell and Molecular Biology, and Section of Integrative Biology, The University of Texas at Austin, Austin, TX, USA. cwilke@mail.utexas.edu
Abstract:
Since the early days of molecular evolution, the conventional wisdom has been that the evolution of protein-coding genes is primarily determined by functional constraints. Yet recent evidence indicates that the evolution of these genes is strongly shaped by the biophysical processes of protein synthesis, protein folding, and specific as well as nonspecific protein-protein interactions. Selection pressures related to these biophysical processes affect primarily the amino-acid sequence of genes, but they also leave their mark on synonymous sites at the nucleotide level. While evidence for specific selection pressures related to protein biophysics is strong, there is currently no unifying framework that integrates the various selection pressures on coding sequences and disentangles their relative importance.
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