Revealing the pervasive landscape of MGE-host interactions in situ with single-cell genomics

Abstract

Mobile genetic elements (MGEs), including plasmids and viruses, drive microbial evolution and ecosystem dynamics, yet their distribution, host range, and functions remain poorly understood, especially among uncultivated lineages. Using [~]60,000 single-cell amplified genomes (SAGs) from host-associated and environmental microbiomes, we identified MGEs internal to or attached to individual cells, directly linking them to their hosts. Between 25% and 75% of cells contained at least one MGE, with gut-derived SAGs showing the highest MGE load. While most MGEs exhibited narrow, species-specific host ranges, a subset spanned multiple species and higher taxonomic ranks. We detected MGE clusters and complete, nearly identical genomes repeatedly associated with hosts across phyla, suggesting both genuinely broad host ranges and recurrent DNA entry events. We also identified microbial species acting as major donors or recipients in antibiotic resistance gene (ARG) exchange, and MGEs, including unclassified types that mediate extensive horizontal transfer of auxiliary functions. Together, these findings illuminate MGE-host associations and underscore that the genetic content of microbial cells is fundamentally linked to their MGEs in nature.