Targeted protein evolution in the gut microbiome by diversity-generating retroelements

Diversity-generating retroelements (DGRs) accelerate evolution by rapidly diversifying variable proteins. The human gastrointestinal microbiota harbors the greatest density of DGRs known in nature, suggesting that they play adaptive roles in this environment. We identified >1100 distinct DGRs among human-associated <i>Bacteroides</i> species and discovered a subset that diversify adhesive components of type V pili and related proteins. We show that <i>Bacteroides</i> DGRs are horizontally transferred across species, display activity levels ranging from high to low, and preferentially alter the functional characteristics of ligand-binding residues on adhesive organelles. Specific variable protein sequences are enriched when <i>Bacteroides</i> strains compete with other commensal bacteria in gnotobiotic mice. Analysis of >2700 DGRs from diverse phyla in mother-infant pairs shows that <i>Bacteroides</i> DGRs are disproportionately transferred to vaginally delivered infants where they actively diversify. Our observations provide a foundation for understanding the potential roles of targeted genome plasticity in shaping host-associated microbial communities.