TY - JOUR T1 - An experimentally determined evolutionary model dramatically improves phylogenetic fit JF - bioRxiv DO - 10.1101/002899 SP - 002899 AU - Jesse D. Bloom Y1 - 2014/01/01 UR - http://biorxiv.org/content/early/2014/02/20/002899.abstract N2 - 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. High-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic analyses. ER -