The human gut microbiome contains many bacterial strains of the same
species (‘strain-level variants’). Describing strains in a biologically
meaningful manner rather than purely taxonomic objects is an important
goal but challenging due to the complexity of strain-level variation.
Here, we measured patterns of co-evolution across >7,000 strains
spanning the bacterial tree-of-life. Using these patterns as a prior for
studying hundreds of gut commensal strains that we isolated, sequenced,
and metabolically profiled revealed widespread structure beneath the
phylogenetic level of species. Defining strains by their co-evolutionary
signatures enabled predicting their metabolic phenotypes and engineering
consortia from strain genome content alone. Our findings demonstrate a
biologically relevant organization to strain-level variation and motivate
a new schema for describing bacterial strains based on their evolutionary
history.