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BIOLOGICAL SCIENCES / EVOLUTION
An empirical test of the concomitantly variable codon hypothesis
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*Department of Ecology, Evolution, and Behavior, University of Minnesota, 100 Ecology Building, 1987 Upper Buford Circle, Saint Paul, MN 55108; and BioTechnology Institute, University of Minnesota, 140 Gortner Laboratory, 1479 Gortner Avenue, Saint Paul, MN 55108
Edited by Daniel L. Hartl, Harvard University, Cambridge, MA, and approved May 17, 2007 (received for review March 1, 2007)
A central assumption of models of molecular evolution, that each site in a sequence evolves independently of all other sites, lacks empirical support. We investigated the extent to which sites evolve codependently in triosephosphate isomerase (TIM), a ubiquitous glycolytic enzyme conserved in both structure and function. Codependencies among sites, or concomitantly variable codons (covarions), are evident from the reduced function and misfolding of hybrid TIM proteins. Although they exist, we find covarions are relatively rare, and closely related proteins are unlikely to have developed them. However, the potential for covarions increases with genetic distance so that highly divergent proteins may have evolved codependencies between many sites. The evolution of covarions undermines a key assumption in phylogenetics and calls into question our ability to disentangle ancient relationships among major taxonomic groups.
covarion | phylogeny | hybrid incompatibilities
Present address: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
To whom correspondence should be addressed. E-mail: deanx024{at}umn.edu
© 2007 by The National Academy of Sciences of the USA
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