Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (233K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (21)
Right arrowRequest Permissions
Citing Articles
Right arrowScopus Links
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Blouin, C.
Right arrow Articles by Roger, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blouin, C.
Right arrow Articles by Roger, A. J.
Related Collections
Right arrow Computational methods
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2003, Vol. 31, No. 2 790-797
© 2003 Oxford University Press

Inferring functional constraints and divergence in protein families using 3D mapping of phylogenetic information

Christian Blouin*, Yan Boucher and Andrew J. Roger

Canadian Institute for Advanced Research, Program in Evolutionary Biology, Genome Atlantic, Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS B3H 4H7, Canada

*To whom correspondence should be addressed. Tel: +1 902 494 2881; Fax: +1 902 494 1355; Email: bongo{at}hades.biochem.dal.ca

Comparative sequence analysis has been used to study specific questions about the structure and function of proteins for many years. Here we propose a knowledge-based framework in which the maximum likelihood rate of evolution is used to quantify the level of constraint on the identity of a site. We demonstrate that site-rate mapping on 3D structures using datasets of rhodopsin-like G-protein receptors and {alpha}- and ß-tubulins provides an excellent tool for pinpointing the functional features shared between orthologous and paralogous proteins. In addition, functional divergence within protein families can be inferred by examining the differences in the site rates, the differences in the chemical properties of the side chains or amino acid usage between aligned sites. Two novel analytical methods are introduced to characterize rate- independent functional divergence. These are tested using a dataset of two classes of HMG-CoA reductases for which only one class can perform both the forward and reverse reaction. We show that functionally divergent sites occur in a cluster of sites interacting with the catalytic residues and that this information should facilitate the design of experimental strategies to directly test functional properties of residues.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Mol Biol EvolHome page
H.-C. Wang, M. Spencer, E. Susko, and A. J. Roger
Testing for Covarion-like Evolution in Protein Sequences
Mol. Biol. Evol., January 1, 2007; 24(1): 294 - 305.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
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]

Home page
 Mol Biol EvolHome page
C. Blouin, D. Butt, and A. J. Roger
Impact of Taxon Sampling on the Estimation of Rates of Evolution at Sites
Mol. Biol. Evol., March 1, 2005; 22(3): 784 - 791.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. J. Keeling and Y. Inagaki
A class of eukaryotic GTPase with a punctate distribution suggesting multiple functional replacements of translation elongation factor 1{alpha}
PNAS, October 26, 2004; 101(43): 15380 - 15385.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
I. Mayrose, D. Graur, N. Ben-Tal, and T. Pupko
Comparison of Site-Specific Rate-Inference Methods for Protein Sequences: Empirical Bayesian Methods Are Superior
Mol. Biol. Evol., September 1, 2004; 21(9): 1781 - 1791.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
B. Pils and J. Schultz
Evolution of the Multifunctional Protein Tyrosine Phosphatase Family
Mol. Biol. Evol., April 1, 2004; 21(4): 625 - 631.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
S. A. Eraly, K. T. Bush, R. V. Sampogna, V. Bhatnagar, and S. K. Nigam
The Molecular Pharmacology of Organic Anion Transporters: from DNA to FDA?
Mol. Pharmacol., March 1, 2004; 65(3): 479 - 487.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
J. L. Paluh, A. N. Killilea, H. W. Detrich 3rd, and K. H. Downing
Meiosis-specific Failure of Cell Cycle Progression in Fission Yeast by Mutation of a Conserved {beta}-Tubulin Residue
Mol. Biol. Cell, March 1, 2004; 15(3): 1160 - 1171.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
S. Gribaldo, D. Casane, P. Lopez, and H. Philippe
Functional Divergence Prediction from Evolutionary Analysis: A Case Study of Vertebrate Hemoglobin
Mol. Biol. Evol., November 1, 2003; 20(11): 1754 - 1759.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.