PAML Advanced Lab

If you have some experience with codon models, and want to try out a tutorial for more advanced materials then use the link below to download an archive for a complete different set of PAML activities. This tutorial focuses on detecting episodic protein evolution via Branch-Site Model A. The tutorial also includes activities about:

  1. detecting MLE instabilities,
  2. carrying out robustness analyses, and
  3. use of smoothed bootstrap aggregation (SBA).

The protocols for each activity are presented in Protocols in Bioinformatics UNIT 6.15. The included PDF file for UNIT 6.16 also presents recommendations for “best practices” when carrying out a large-scale evolutionary survey for episodic adaptive evolution by using PAML. The files required for this “alternative lab” are available via a Bitbucket repository.



Large-scale evolutionary surveys are now commonplace. But with the use of progressively more complex codon models, these surveys are fraught with perils. Complex models are more prone to statistical problems such as MLE irregularities, and some can be quite sensitive to model misspecification. UNIT 6.16 (see above) provides some recommended “best practices” for a 2-phase approach to quality control and robustness in evolutionary surveys. We have applied these to a large scale survey for functional divergence in nuclear receptors during homing evolution, and we used experimental approaches to investigate hypotheses about the role of a particular nuclear receptor (NR2C1) as a key modulator of developmental pluripotnetiality during hominid evolution. The paper below illustrates the power of such an evolutionary survey, and the importance of an experimental design that has explicit protocols for “best practices”.

Example large-scale survey