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There are numerous phylogenetic reconstruction methods and models available—but which should you use and why? Important considerations in phylogenetic analyses include data quality, structure, signal, alignment length and sampling. If poorly modelled, variation in rates of change across proteins and across lineages can lead to incorrect phylogeny reconstruction which can then lead to downstream misinterpretation of the underlying data. The risk of choosing and applying an inappropriate model can be reduced with some critical yet straightforward steps outlined in this paper. We use the question of the position of the root of placental mammals as our working example to illustrate the topological impact of model misspecification. Using this case study we focus on using models in a Bayesian framework and we outline the steps involved in identifying and assessing better fitting models for specific datasets.

A Guide to Phylogenetic Reconstruction Using Heterogeneous Models—A Case Study from the Root of the Placental Mammal Tree