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.
by Jesse Bloom, FHCRC. I had no idea he was doing this, and talk to him on a regular basis!