title: Site interdependence attributed to tertiary structure in amino acid sequence evolution.
abstract: Standard likelihood-based frameworks in phylogenetics consider the process of evolution of a sequence site by site. Assuming that sites evolve independently greatly simplifies the required calculations. However, this simplification is known to be incorrect in many cases. Here, a computational method that allows for general dependence between sites of a sequence is investigated. Using this method, measures acting as sequence fitness proxies can be considered over a phylogenetic tree. In this work, a set of statistically derived amino acid pairwise potentials, developed in the context of protein threading, is used to account for what we call the structural fitness of a sequence. We describe a model combining statistical potentials with an empirical amino acid substitution matrix. We propose such a combination as a useful way of capturing the complexity of protein evolution. Finally, we outline features of the model using three datasets and show the approach's sensitivity to different tree topologies.
authors.affiliation: Canadian Institute for Advanced Research, Département de biochimie, Université de Montréal, Montréal, Canada. nicolas.rodrigue@umontreal.ca
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodrigue
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lartillot
authors.forename: David
authors.initials: D
authors.lastname: Bryant
authors.forename: Hervé
authors.initials: H
authors.lastname: Philippe
mesh_terms: D000595:Amino Acid Sequence; D001499:Bayes Theorem; D019295:Computational Biology / Q000379:methods; D019143:Evolution, Molecular; D016013:Likelihood Functions; D008954:Models, Biological; D009010:Monte Carlo Method; D010802:Phylogeny; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*
chemical_list: D011506:Proteins