A likelihood ratio test for evolutionary rate shifts and functional divergence among proteins
- *Bioinformatics Research Center, University of Aarhus, Høegh Guldbergsgade 10, Building 090, DK-8000 Århus C, Denmark; and ‡Department of Zoology, Box 118525, University of Florida, Gainesville, FL 32611-8525
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Communicated by Walter M. Fitch, University of California, Irvine, CA (received for review July 9, 2001)
Abstract
Changes in protein function can lead to changes in the selection acting on specific residues. This can often be detected as evolutionary rate changes at the sites in question. A maximum-likelihood method for detecting evolutionary rate shifts at specific protein positions is presented. The method determines significance values of the rate differences to give a sound statistical foundation for the conclusions drawn from the analyses. A statistical test for detecting slowly evolving sites is also described. The methods are applied to a set of Myc proteins for the identification of both conserved sites and those with changing evolutionary rates. Those positions with conserved and changing rates are related to the structures and functions of their proteins. The results are compared with an earlier Bayesian method, thereby highlighting the advantages of the new likelihood ratio tests.
Footnotes
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↵ † To whom reprint requests should be addressed. E-mail: bk{at}birc.dk.
- Abbreviations:
- LRT,
- likelihood ratio test;
- ML,
- maximum likelihood;
- bHLHZip,
- basic helix–loop–helix leucine zipper
- Copyright © 2001, The National Academy of Sciences
