title: An empirical test of the concomitantly variable codon hypothesis.
abstract: 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.
authors.affiliation: Department of Ecology, Evolution, and Behavior, University of Minnesota, 100 Ecology Building, 1987 Upper Buford Circle, Saint Paul, MN 55108, USA.
authors.forename: Lauren M F
authors.initials: LM
authors.lastname: Merlo
authors.forename: Mark
authors.initials: M
authors.lastname: Lunzer
authors.forename: Antony M
authors.initials: AM
authors.lastname: Dean
mesh_terms: D003062:Codon / Q000235:genetics*; D036262:Empirical Research; D019143:Evolution, Molecular; D008957:Models, Genetic; D010802:Phylogeny; D014305:Triose-Phosphate Isomerase / Q000235:genetics
chemical_list: D003062:Codon; D014305:Triose-Phosphate Isomerase