How does MEME infer episodic selection?

Mixed Effects Model of Evolution (MEME) is a generalization of FEL, with the first two phases of the analyses being identical. Whereas FEL assumes that the same dN/dS (ω) ratio applies to all branches (or in the case of IFEL - to interior branches), MEME instead models variable ω across lineages at an individual site (i.e. each site is treated is a FIXED effects component of the model) using a two-bin random distribution with ω^-≤1 (proportion p) and ω⁺ (unrestriced, proportion 1-p).

This can be interpreted as having a proportion (p) of branches at a site evolve neutrally or under negative selection, while the remained (1-p) can also evolve under diversifying selection. To test for evidence of episodic selection, we construct the likelihood ratio test between the above model (alternative) and the nested null, where ω⁺ is forced to be in [0,1].

Simulations (manuscript in preparation) show that MEME is nearly always preferable to FEL because it matches the performance of FEL when there is no lineage-to-lineage variation in dN/dS, and significantly improves upon it when such variation is present. For instance, if one clade in a large tree is evolving with dN/dS = 5, while the rest of the tree (say 90% of branches) evolve with dN/dS = 0.1, FEL is likely to call such site NEGATIVELY selected, whilst MEME will detect that a small proportion of branches is evolving subject to positive selection.

The details of the algorithm to efficiently compute the phylogenetic likelihood function in this context and further model background can be found in this Molecular Biology and Evolution paper