title: Heterotachy, an important process of protein evolution.
abstract: Because of functional constraints, substitution rates vary among the positions of a protein but are usually assumed to be constant at a given site during evolution. The distribution of the rates across the sequence positions generally fits a Gamma distribution. Models of sequence evolution were accordingly designed and led to improved phylogenetic reconstruction. However, it has been convincingly demonstrated that the evolutionary rate of a given position is not always constant throughout time. We called such within-site rate variations heterotachy (for "different speed" in Greek). Yet, heterotachy was found among homologous sequences of distantly related organisms, often with different functions. In such cases, the functional constraints are likely different, which would explain the different distribution of variable sites. To evaluate the importance of heterotachy, we focused on amino acid sequences of mitochondrial cytochrome b, for which the function is likely the same in all vertebrates. Using 2,038 sequences, we demonstrate that 95% of the variable positions are heterotachous, i.e., underwent dramatic variations of substitution rate among vertebrate lineages. Heterotachy even occurs at small evolutionary scale, and in these cases it is very unlikely to be related to functional changes. Since a large number of sequences are required to efficiently detect heterotachy, the extent of this phenomenon could not be estimated for all proteins yet. It could be as large as for cytochrome b, since this protein is not a peculiar case. The observations made here open several new avenues of research, such as the understanding of the evolution of functional constraints or the improvement of phylogenetic reconstruction methods.
authors.affiliation: Phylogénie, Bioinformatique et Génome, CNRS, Université Pierre et Marie Curie, 9, quai St. Bernard, 75005 Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Lopez
authors.forename: D
authors.initials: D
authors.lastname: Casane
authors.forename: H
authors.initials: H
authors.lastname: Philippe
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002965:Classification; D019295:Computational Biology; D003198:Computer Simulation; D003573:Cytochrome b Group / Q000737:chemistry; D019143:Evolution, Molecular; D008958:Models, Molecular; D010802:Phylogeny; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000145:classification; D013329:Structure-Activity Relationship
chemical_list: D003573:Cytochrome b Group; D011506:Proteins