PT  - JOURNAL ARTICLE
AU  - Jesse D. Bloom
TI  - An experimentally determined evolutionary model dramatically improves phylogenetic fit
AID  - 10.1101/002899
DP  - 2014 Jan 01
TA  - bioRxiv
PG  - 002899
4099  - http://biorxiv.org/content/early/2014/03/05/002899.short
4100  - http://biorxiv.org/content/early/2014/03/05/002899.full
AB  - 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.