An Experimentally Determined Evolutionary Model Dramatically Improves Phylogenetic Fit

作者：Bloom Jesse D^*

来源：Molecular Biology and Evolution, 2014, 31(8): 1956-1978.

DOI：10.1093/molbev/msu173

• phylogenetics
• codon model
• substitution model
• influenza
• nucleoprotein
• deep mutational scanning

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.

• 出版日期2014-8