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

Macadangdang, B. R.; Wang, Y.; Woodward, C.; Revilla, J. I.; Shaw, B. M.; Sasaninia, K.; Makanani, S. K.; Berruto, C.; Miller, J. F.

doi:10.1101/2024.11.15.621889

bioRxiv · 10.1101/2024.11.15.621889

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

Macadangdang, B. R.·Wang, Y.·Woodward, C.·Revilla, J. I.·Shaw, B. M.·Sasaninia, K.·Makanani, S. K.·Berruto, C.·Miller, J. F.

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Abstract

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 they play adaptive roles in this environment. We identified >1,100 unique DGRs among human-associated Bacteroides species and discovered a subset that diversify adhesive components of Type V pili and related proteins. We show that Bacteroides DGRs are horizontally transferred across species, that some are highly active while others are tightly controlled, and that they preferentially alter the functional characteristics of ligand-binding residues on adhesive organelles. Specific variable protein sequences are enriched when Bacteroides strains compete with other commensal bacteria in gnotobiotic mice. Analysis of >2,700 DGRs from diverse phyla in mother-infant pairs shows that Bacteroides DGRs are preferentially transferred to vaginally delivered infants where they actively diversify. Our observations provide a foundation for understanding the roles of stochastic, targeted genome plasticity in shaping host-associated microbial communities.

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Macadangdang, B. R., Wang, Y., Woodward, C., Revilla, J. I., Shaw, B. M., Sasaninia, K., Makanani, S. K., Berruto, C., Miller, J. F.. 2024-11-16. Targeted protein evolution in the gut microbiome by diversity-generating retroelements. https://doi.org/10.1101/2024.11.15.621889

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