Phylogenetic tree estimation with and without alignment: new distance methods and benchmarking

Phylogenetic tree inference is a critical component of many systematic and evolutionary studies. The majority of these studies are based on the two-step process of multiple sequence alignment followed by tree inference, despite persistent evidence that the alignment step can lead to biased results. Here we present a two-part study that first presents PaHMM-Tree, a novel neighbour joining-based method that estimates pairwise distances without assuming a single alignment. We then use simulations to benchmark its performance against a wide-range of other phylogenetic tree inference methods, including the first comparison of alignment-free distance-based methods against more conventional tree estimation methods. Our new method for calculating pairwise distances based on statistical alignment provides distance estimates that are as accurate as those obtained using standard methods based on the true alignment. Pairwise distance estimates based on the two-step process tend to be substantially ...