title: Site-specific evolutionary rate inference: taking phylogenetic uncertainty into account.
abstract: The evolutionary rate at an amino acid site is indicative of how conserved this site is and, in turn, allows evaluating the importance of this site in maintaining the structure/function of the protein. When evolutionary rates are estimated, one must reconstruct the phylogenetic tree describing the evolutionary relationship among the sequences under study. However, if the inferred phylogenetic tree is incorrect, it can lead to erroneous site-specific rate estimates. Here we describe a novel Bayesian method that uses Markov chain Monte Carlo methodology to integrate over the space of all possible trees and model parameters. By doing so, the method considers alternative evolutionary scenarios weighted by their posterior probabilities. We show that this comprehensive evolutionary approach is superior over methods that are based on only a single tree. We illustrate the potential of our algorithm by analyzing the conservation pattern of the potassium channel protein family.
authors.affiliation: Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
authors.forename: Itay
authors.initials: I
authors.lastname: Mayrose
authors.forename: Amir
authors.initials: A
authors.lastname: Mitchell
authors.forename: Tal
authors.initials: T
authors.lastname: Pupko
mesh_terms: D000465:Algorithms; D019943:Amino Acid Substitution / Q000235:genetics*; D001499:Bayes Theorem; D003198:Computer Simulation; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D008390:Markov Chains; D008957:Models, Genetic; D008958:Models, Molecular; D009010:Monte Carlo Method; D010802:Phylogeny; D015221:Potassium Channels / Q000235:genetics
chemical_list: D015221:Potassium Channels