Fig. 2. Example of how phylogenomics can guide the experimental analysis of virulence determinants.

The evolution of virulence in strains of oral polio vaccine (OPV)⁸. OPV is an attenuated form of poliovirus that can occasionally revert to a virulent form and cause outbreaks of poliomyelitis. A | Phylogenetic analysis of OPV strains in nature reveals that some mutations associated with high virulence have experienced more frequent parallel evolution than expected by chance (and occupy well supported nodes) and hence are likely to be seletively favoured⁸. B | Computational evolutionary analysis then reveals that this parallel evolution for high virulence is associated with a hypothetical threonine-to-proline (T-to-P) amino acid change that is subject to significant adaptive evolution (which can be detected in a variety of ways)^60,63. C | The virulence impact of these mutations is then confirmed in both in vitro (cell culture; part Ca) and in vivo (mouse; part Cb) experimental studies. In all cases, the red shading signifies increased virulence.