The landscape of novel lateral gene transfer events in the human microbiome

Lateral gene transfer (LGT) is an important mechanism for genome diversification in microbial communities, including the human microbiome. While previous efforts have cataloged LGT in human-associated microbial isolate genomes, directly identifying novel (and potentially recent) LGT events in human microbiomes is an open challenge. To address this, we developed a computational method (WAAFLE) to identify novel LGT events from assembled metagenomes. We applied WAAFLE to ~2K diverse human metagenomes, identifying ~100K high confidence, novel LGT events. These events were enriched for mobile element, restriction-modification, and transport functions, and their frequency was influenced by biogeography, phylogenetic relatedness, and the ecological abundance of donor taxa. These trends manifested as LGT networks in which abundant hub taxa donate unequally with their close phylogenetic neighbors. Our findings suggest that LGT is an active process in the human microbiome.