title: An experimentally determined evolutionary model dramatically improves phylogenetic fit.
abstract: All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.
authors.affiliation: Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA jbloom@fhcrc.org.
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Bloom
mesh_terms: D000465:Algorithms; D003062:Codon; D019143:Evolution, Molecular; D059014:High-Throughput Nucleotide Sequencing; D008957:Models, Genetic; D008969:Molecular Sequence Data; D059645:Mutation Rate; D009975:Orthomyxoviridae / Q000378:metabolism*; D010802:Phylogeny; D014758:Viral Core Proteins / Q000235:genetics*
chemical_list: D003062:Codon; D014758:Viral Core Proteins
keywords: codon model; deep mutational scanning; influenza; nucleoprotein; phylogenetics; substitution model