Low-cost genomics enable high-throughput isolate screening and strain-level microbiome profiling

Earths environments harbor complex consortia of microbial lineages that affect processes ranging from host health to biogeochemical cycles. However, understanding the evolution and function of these microbiota has been limited by an inability to isolate individual microbial constituents and assemble their complete genomes in a high-throughput manner. Here, we present a workflow for bacterial isolation and whole-genome sequencing from complex microbiota using open-source labware and the OpenTrons automated liquid handling robotics platform. Our approach circumvents the need for isolate screening (e.g., through 16S rDNA sequencing or mass spectrometry analyses) by reducing the costs of genome-sequencing to ~$10 per bacterium. Applying the workflow, we quantified genomic diversity within 45 bacterial species in the chimpanzee gut microbiota. Results revealed hotspots of recombination in bacterial genomes and elevated transmission of plasmids between distantly related bacterial species within individual chimpanzee hosts. This study develops and applies an approach for high-throughput bacterial isolation and genome sequencing, enabling population genetic analyses of bacterial strains within complex communities not currently possible with metagenomic data alone.