Capturing microbial genome dynamics in the human gut using Hi-C

Horizontal gene transfer is responsible for modifying the genetic potential of microbes across different time-scales, yet current methods are limited in their ability to directly link mobile genetic elements and their microbial hosts in complex ecosystems such as the human gut. We apply Hi-C (high-resolution chromosome conformation capture), coupled with rigorous probabilistic modeling, to achieve a strain-level resolution of human gut microbiota genomes, from a single sample and without the use of reference genomes. By applying this method to samples from two healthy individuals we recovered 88 semi-complete genomes. Comparison to species-level reference genomes identified 47,928 strain-specific accessory genes (12,251 accessory elements) with a strong mobility signature that make up on average 19.5% of each genome. Analysis of samples from the same individual taken 10 years apart supports rapid in situ gene transfer and suggests that the mean half-life of an accessory gene in the human gut is between 11 and 88 years.