Phylogenetic Placement of Aligned Genomes and Metagenomes With Non-Tree-Like Evolutionary Histories

Phylogenetic placement is the computational task that places a query taxon into a reference phylogeny by analyzing biomolecular sequences or other evolutionary characters. A chief advantage of phylogenetic placement over traditional phylogenetic reconstruction is computational scalability, and the former has many applications in phylogenetics and beyond. Existing phylogenetic placement methods share the common simplifying assumption that a phylogenetic tree suffices for modeling evolutionary history. However, a growing body of research indicates that non-tree-like evolution is prevalent throughout the Tree of Life - the evolutionary history of all life on Earth - which in fact may not be a tree at all. More general graph representations such as phylogenetic networks have therefore been proposed, and a new generation of phylogenetic network reconstruction methods are under active development. But the simplifying assumption made by phylogenetic tree placement methods is fundamentally at odds with the non-tree-like evolutionary histories of many microbes and other organisms. The consequences of this conflict are poorly understood. In this study, we conduct a comprehensive performance study to directly assess the impact of non-tree-like evolution on phylogenetic tree placement of genomes and metagenomes. Our study includes in silico simulation experiments as well as empirical data analyses. We find that the topological accuracy of phylogenetic tree placement degrades quickly as genomic sequence evolution becomes increasingly non-tree-like. We then introduce NetPlacer, a new statistical method for phylogenetic network placement of genomes and metagenomes. Initial experiments with NetPlacer provide a proof-of-concept, but also point to the need for greater computational scalability.