MBE Advance Access published online on June 27, 2003
Molecular Biology and Evolution, doi:10.1093/molbev/msg171
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2003; all rights reserved
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Phylogénie, Bioinformatique et Génome, UMR 7622 CNRS, Université Pierre et Marie Curie, 9, Quai St Bernard - 75005 Paris - France
* To whom correspondence should be addressed. E-mail: herve.philippe{at}umontreal.ca.
It is a central assumption of evolution that gene duplications provide the genetic raw-material to create proteins with new functions. The increasing availability in multigene family sequences that has resulted from genome projects has inspired the creation of novel in silico approaches to predict details of protein function. The underlying principle of all such approaches is to compare the evolutionary properties of homologous sequence positions in paralogous proteins. It has been proposed that the positions that show switches in substitution rate over time -i.e., 'heterotachous sites'- are good indicators of functional divergence. Here, we analyzed the Key Words:
Covarion, Evolutionary rate, Hemoglobin, Heterotachy, Protein function, Tertiary structures
© 2003 Society for Molecular Biology and Evolution
Original Articles
Functional Divergence Prediction from Evolutionary Analysis: A Case Study of Vertebrate Hemoglobin
Abstract 
and 
paralogous subunits of hemoglobin in search for such signatures. We found as many heterotachous sites in comparisons between groups of paralogous subunits (/) as between orthologous ones (/, /). Thus, the importance of substitution rate shifts as predictors of specialization between protein subfamilies might be reconsidered. Instead, such shifts may reflect a more general process of protein evolution, consistent with the fact that they can be compatible with function conservation. As an alternative, we focused on those residues showing highly constrained states in two sequence groups, but different in each group, and we named them CBD (for Constant But Different). As opposed to heterotachous positions, CBD sites were markedly over-represented in paralogous (/) than in orthologous (/, /) comparisons, indicating them as likely signatures of functional specialization between the two subunits. Consistently, when superimposed onto the three-dimensional structure of hemoglobin, CBD positions appeared to cluster preferentially on inter-subunit surfaces, two contact areas crucial to function in vertebrate tetrameric hemoglobin. The identification and analysis of CBD sites by complementing structural information with evolutionary data may represent a promising direction to future studies dealing with the functional characterization of an ever increasing number of multi-gene families identified by complete genome analyses.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Georgelis, J. R. Shaw, and L. C. Hannah Phylogenetic Analysis of ADP-Glucose Pyrophosphorylase Subunits Reveals a Role of Subunit Interfaces in the Allosteric Properties of the Enzyme Plant Physiology, September 1, 2009; 151(1): 67 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Marshall, C. Simon, and T. R. Buckley Accurate Branch Length Estimation in Partitioned Bayesian Analyses Requires Accommodation of Among-Partition Rate Variation and Attention to Branch Length Priors Syst Biol, December 1, 2006; 55(6): 993 - 1003. [Full Text] [PDF]
|
|
|
|
 |
|
 X. Gu A Simple Statistical Method for Estimating Type-II (Cluster-Specific) Functional Divergence of Protein Sequences Mol. Biol. Evol., October 1, 2006; 23(10): 1937 - 1945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Abhiman, C. O. Daub, and E. L. L. Sonnhammer Prediction of Function Divergence in Protein Families Using the Substitution Rate Variation Parameter Alpha Mol. Biol. Evol., July 1, 2006; 23(7): 1406 - 1413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Gadagkar and S. Kumar Maximum Likelihood Outperforms Maximum Parsimony Even When Evolutionary Rates Are Heterotachous Mol. Biol. Evol., November 1, 2005; 22(11): 2139 - 2141. [Abstract] [Full Text] [PDF]
|
|