Journal of Molecular Evolution

, Volume 56, Issue 3, pp 243–254 | Cite as

Connectivity of Neutral Networks, Overdispersion, and Structural Conservation in Protein Evolution

  • Ugo Bastolla
  • Markus Porto
  • Markus H. Eduardo Roman
  • Michele H. Vendruscolo

Abstract

Protein structures are much more conserved than sequences during evolution. Based on this observation, we investigate the consequences of structural conservation on protein evolution. We study seven of the most studied protein folds, determining that an extended neutral network in sequence space is associated with each of them. Within our model, neutral evolution leads to a non-Poissonian substitution process, due to the broad distribution of connectivities in neutral networks. The observation that the substitution process has non-Poissonian statistics has been used to argue against the original Kimura neutral theory, while our model shows that this is a generic property of neutral evolution with structural conservation. Our model also predicts that the substitution rate can strongly fluctuate from one branch to another of the evolutionary tree. The average sequence similarity within a neutral network is close to the threshold of randomness, as observed for families of sequences sharing the same fold. Nevertheless, some positions are more difficult to mutate than others. We compare such structurally conserved positions to positions conserved in protein evolution, suggesting that our model can be a valuable tool to distinguish structural from functional conservation in databases of protein families. These results indicate that a synergy between database analysis and structurally based computational studies can increase our understanding of protein evolution.

Neutral evolution Non-Poissonian substitution process Conserved protein residues 

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Copyright information

© Springer-Verlag New York Inc. 2003

Authors and Affiliations

  • Ugo Bastolla
    • 1
  • Markus Porto
    • 2
  • Markus H. Eduardo Roman
    • 3
  • Michele H. Vendruscolo
    • 4
  1. 1., Centro de Astrobiología (INTA-CSIC), c. tra de Ajalvir km. 4, 28850 Torrejon de Ardoz, Spain
  2. 2., Max-Planck-Institut für Physik komplexer Systeme, 01187 Dresden, Germany
  3. 3.Dipartimento di Fisica, Università di Milano, 20133 Milano, Italy
  4. 4.University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK

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