On the causes of evolutionary transition:transversion bias

Arlin Stoltzfus; Ryan W. Norris

EX and U are used on the grounds of being powerful and mutationally unbiased predictors, whereas various biochemical predictors are less powerful (as will become apparent below), and various evolution-based measures other than U (e.g., PAM, . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/027722 doi: bioRxiv preprint BLOSUM), though perhaps powerful, cannot be used, because they are not known to be free of the mutational effects that we wish to exclude. The EX matrix, based on a meta-analysis of early mutation studies (which reported phenotypes other than fitness), was designed specifically to serve as a mutationally unbiased measure of exchangeability in models that separate selection from mutation. In a comparative evaluation, EX was shown to be as powerful, or more powerful, than a representative sample of other predictors (Yampolsky and Stoltzfus 2005) . The "universal evolutionary index" or U matrix of Tang, et al (2004) is based on modeling evolution of thousands of genes, using a method designed to separate codon-level mutational effects from protein-level effects. It purports to be a measure of evolutionary acceptability that scales directly with the rate of evolution.