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.

Phylogenomics and the reconstruction of the tree of life

“…In addition, the confounding effects on phylogenetic inference of heterotachy 113 (variation of evolutionary rate through time) are only now beginning to be better understood…”

Cell evolution and Earth history: stasis and revolution

“…Second, some genes can occasionally be transferred laterally among unrelated organisms, so their tree partially reflects horizontal transfer of individual genes, not vertical phylogeny of the organisms containing them (Philippe & Douady 2003;Lerat et al 2005). Third, systematic biases in evolutionary rates and modes of virtually all genes in at least parts of the tree can make the branching order partly incorrect (Gribaldo & Philippe 2002;Lopez et al 2002). Problems of random error through insufficient sequence sampling and misleading lateral transfers can be largely solved by making trees from several or many different genes.…”

“…in sequence evolutionary rates or modes among taxa or biases shared by many genes (Gribaldo & Philippe 2002;Lopez et al 2002). Such problems are more widespread than assumed in the early days of tree reconstruction.…”

Why coelacanths are not ‘living fossils’

“…They do not have an extremely long generation time, and we have previously discussed that they definitely do not form large populations [13]. In addition, it is well known that substitution rates vary across a genome depending on several factors, such as the local recombination rate and distance to the origin of replication; it is also known that substitution rates are not constant across lineages [34][35][36]. In addition, it is likely that amino acid interactions are very important in variation in the rate of protein evolution in different lineages [37].…”