Subspecies phylogeny in the human gut revealed by co-evolutionary constraints across the bacterial kingdom.

The human gut microbiome contains many bacterial strains of the same species ("strain-level variants") that shape microbiome function. The tremendous scale and molecular resolution at which microbial communities are being interrogated motivates addressing how to describe strain-level variants. We introduce the "Spectral Tree"-an inferred tree of relatedness built from patterns of co-evolutionary constraint between greater than 7,000 diverse bacteria. Using the Spectral Tree to describe over 600 diverse gut commensal strains that we isolated, whole-genome sequenced, and metabolically profiled revealed (1) widespread phylogenetic structure among strain-level variants, (2) the origins of subspecies phylogeny as a shared history of phage infections across humans, and (3) the key role of inter-human strain variation in predicting strain-level metabolic qualities. Overall, our work demonstrates the existence and metabolic importance of structured phylogeny below the level of species for commensal gut bacteria, motivating a redefinition of individual strains according to their evolutionary context. A record of this paper's transparent peer review process is included in the supplemental information.