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.