Using Evolutionary Rates to Investigate Protein Functional Divergence and Conservation: A Case Study of the Carbonic Anhydrases

Using Evolutionary Rates to Investigate Protein Functional Divergence and Conservation: A Case Study of the Carbonic Anhydrases

Bjarne Knudsen^a, Michael M. Miyamoto^b, Philip J. Laipis^c, and David N. Silverman^d
^a Bioinformatics Research Center, University of Aarhus, 8000 Århus C, Denmark,
^b Department of Zoology, University of Florida, Gainesville, Florida 32611-8525,
^c Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida 32610-0245
^d Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida 32610-0267

Corresponding author: Bjarne Knudsen, Box 118525, University of Florida, Gainesville, FL 32611-8525., knudsen{at}zoo.ufl.edu (E-mail)

Communicating editor: J. HEIN

Functional constraints on proteins limit their evolutionaryrates at specific sites. These constraints allow for the interpretationof conserved residues and sites with a rate change as thosemost likely underlying the functional similarities and differencesamong protein subfamilies, respectively. This study describesnew likelihood-ratio tests (LRTs) that complement existing onesfor the identification of both conserved and rate change sites.These identifications are validated by the recovery of residuesthat are known from existing biochemical and structural informationto be critical for the functional similarities and differencesamong carbonic anhydrases (CAs). In combination with this otherinformation, these LRTs also support a unique antioxidant defenserole for the puzzling CA III. As illustrated by the CAs, theseLRTs, in combination with other biological evidence, offer apowerful and cost-effective approach for testing hypotheses,making predictions, and designing experiments in protein functionalstudies.

This article has been cited by other articles:

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]

C.-H. Huang and J. Peng
Evolutionary conservation and diversification of Rh family genes and proteins
PNAS, October 25, 2005; 102(43): 15512 - 15517.
[Abstract] [Full Text] [PDF]

C. Guillet-Claude, N. Isabel, B. Pelgas, and J. Bousquet
The Evolutionary Implications of knox-I Gene Duplications in Conifers: Correlated Evidence from Phylogeny, Gene Mapping, and Analysis of Functional Divergence
Mol. Biol. Evol., December 1, 2004; 21(12): 2232 - 2245.
[Abstract] [Full Text] [PDF]

Z. Zhang and H. Kishino
Genomic Background Predicts the Fate of Duplicated Genes: Evidence From the Yeast Genome
Genetics, April 1, 2004; 166(4): 1995 - 1999.
[Abstract] [Full Text] [PDF]

				C.-H. Huang and J. Peng Evolutionary conservation and diversification of Rh family genes and proteins PNAS, October 25, 2005; 102(43): 15512 - 15517. [Abstract] [Full Text] [PDF]

				C. Guillet-Claude, N. Isabel, B. Pelgas, and J. Bousquet The Evolutionary Implications of knox-I Gene Duplications in Conifers: Correlated Evidence from Phylogeny, Gene Mapping, and Analysis of Functional Divergence Mol. Biol. Evol., December 1, 2004; 21(12): 2232 - 2245. [Abstract] [Full Text] [PDF]

				Z. Zhang and H. Kishino Genomic Background Predicts the Fate of Duplicated Genes: Evidence From the Yeast Genome Genetics, April 1, 2004; 166(4): 1995 - 1999. [Abstract] [Full Text] [PDF]