Journal Article

Protein Structural Modularity and Robustness Are Associated with Evolvability

Mary M. Rorick and Günter P. Wagner

in Genome Biology and Evolution

Published on behalf of Society for Molecular Biology and Evolution

Volume 3, issue , pages 456-475
Published in print January 2011 |
Published online May 2011 | e-ISSN: 1759-6653 | DOI:

More Like This

Show all results sharing these subjects:

  • Bioinformatics and Computational Biology
  • Evolutionary Biology
  • Genetics and Genomics


Show Summary Details


Theory suggests that biological modularity and robustness allow for maintenance of fitness under mutational change, and when this change is adaptive, for evolvability. Empirical demonstrations that these traits promote evolvability in nature remain scant however. This is in part because modularity, robustness, and evolvability are difficult to define and measure in real biological systems. Here, we address whether structural modularity and/or robustness confer evolvability at the level of proteins by looking for associations between indices of protein structural modularity, structural robustness, and evolvability. We propose a novel index for protein structural modularity: the number of regular secondary structure elements (helices and strands) divided by the number of residues in the structure. We index protein evolvability as the proportion of sites with evidence of being under positive selection multiplied by the average rate of adaptive evolution at these sites, and we measure this as an average over a phylogeny of 25 mammalian species. We use contact density as an index of protein designability, and thus, structural robustness. We find that protein evolvability is positively associated with structural modularity as well as structural robustness and that the effect of structural modularity on evolvability is independent of the structural robustness index. We interpret these associations to be the result of reduced constraints on amino acid substitutions in highly modular and robust protein structures, which results in faster adaptation through natural selection.

Keywords: modularity; designability; contact density; evolvability; protein evolution; robustness

Journal Article.  10734 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology ; Evolutionary Biology ; Genetics and Genomics

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.