Tracking microbial evolution in the human gut using Hi-C reveals extensive horizontal gene transfer, persistence, and adaptation

Despite the importance of horizontal gene transfer for rapid bacterial evolution, reliable assignment of mobile genetic elements to their microbial hosts in natural communities such as the human gut microbiota remains elusive. We used Hi-C (High-throughput chromosomal conformation capture), coupled with probabilistic modeling of experimental noise, to resolve 88 strain-level metagenome-assembled genomes of distal gut bacteria from two subjects, including 12,251 accessory elements. Comparisons of 2 samples collected 10 years apart for each of the subjects revealed extensive in situ exchange of accessory elements, as well as evidence of adaptive evolution in core genomes. Accessory elements were predominantly promiscuous and prevalent in the distal gut metagenomes of 218 adult subjects. This work provides a foundation and approach for studying microbial evolution in natural environments.