Calculating site-specific evolutionary rates at the amino-acid or codon level yields similar rate estimates

Abstract

Site-specific evolutionary rates can be estimated from codon sequences or from amino-acid sequences. For codon sequences, the most popular methods use some variation of the dN∕dS ratio. For amino-acid sequences, one widely-used method is called Rate4Site, and it assigns a relative conservation score to each site in an alignment. How site-wise dN∕dS values relate to Rate4Site scores is not known. Here we elucidate the relationship between these two rate measurements. We simulate sequences with known dN∕dS, using either dN∕dS models or mutation–selection models for simulation. We then infer Rate4Site scores on the simulated alignments, and we compare those scores to either true or inferred dN∕dS values on the same alignments. We find that Rate4Site scores generally correlate well with true dN∕dS, and the correlation strengths increase in alignments with greater sequence divergence and more taxa. Moreover, Rate4Site scores correlate very well with inferred (as opposed to true) dN∕dS values, even for small alignments with little divergence. Finally, we verify this relationship between Rate4Site and dN∕dS in a variety of empirical datasets. We conclude that codon-level and amino-acid-level analysis frameworks are directly comparable and yield very similar inferences.

mtProtEvol: the resource presenting molecular evolution analysis of proteins involved in the function of Vertebrate mitochondria

“…Therefore, for the analysis of the RSA evolution it is necessarily to take into account the family-wise rate of protein evolution. Additionally, it was shown that site-specific evolutionary rates at the level of amino-acids are very similar with such estimations on codon level [36]. Considering this, it is tempting to compare the evolutionary rates of amino acid replacements with the rates of RSA evolutionary changes.…”

“…At the same time, it was shown that the evolution of natural proteins is often associated with lowering stability against misfolding, which in turn can shuffle parts of the globule with respect to the solvent [34]. New software and models have been developed to detect positive selection of protein coding genes [33] and proteins [36] based on these observations. Finally, it was recently shown, that the acceleration of mutation fixations in various protein families could fundamentally change the accepted pattern of mutation fixations including permittance of fixations with strong RSA changes [35].…”

Do some viruses use growth hormone, prolactin and their receptors to facilitate entry into cells?

“…Figure 2a illustrates evolutionary trees for mature (lacking signal peptide) mammalian GH based on non‐synonymous (dN) and synonymous substitutions (dS) (Box 1). For most of the dN tree (equivalent to a tree based on protein sequence [ 20 ] ) the sequence is strongly conserved, reflecting a low basal rate of evolution, seen, for example, in pig, rabbit and all Carnivora. However, the rate of evolution increases markedly on several occasions.…”

Relative Evolutionary Rates in Proteins Are Largely Insensitive to the Substitution Model

“…In the context of protein sequence analysis, low site-specific substitution rates have served as a proxy for evolutionary conservation. Similarly, high rates have been regarded as a correlate of adaptation or positive selection ( Sydykova and Wilke 2017 ). Positions which play key roles in protein functions, including those involved in protein–protein or protein–ligand interactions or those at or near active regions, tend to evolve very slowly and are highly conserved ( Echave et al.…”