Abstract
Bacteria inhabiting the human body vary in genome size by over an order of magnitude, but the processes that generate this diversity are poorly understood. Here, we show that evolutionary forces drive divergence in genome size between bacterial lineages in the gut and their closest relatives in other body sites. Analyses of thousands of reference bacterial isolate genomes and metagenome-assembled genomes from the human microbiome indicated that transitions into the gut from other body sites have promoted genomic expansions, whereas the opposite transitions have promoted genomic contractions. Bacterial genomes in the gut are on average ∼127 kb larger than their closest congeneric relatives from other body sites. Moreover, genome size and relative abundance are positively associated within the gut but negatively associated at other body sites. These results indicate that the gut microbiome promotes expansions of bacterial genomes relative to other body sites.