# An experimentally determined evolutionary model dramatically improves phylogenetic fit

## TL;DR

A new experimental approach creates a more accurate model of gene evolution for phylogenetics, outperforming traditional models.

## Contribution

A parameter-free evolutionary model is experimentally determined, improving phylogenetic accuracy.

## Key findings

- The new model for influenza nucleoprotein outperforms existing models with many parameters.
- High-throughput experimental strategies provide novel data for phylogenetic analysis.
- Site-heterogeneous selection is better captured through experimental determination.

## 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. 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.