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

Benjamin R Macadangdang1,2, Yanling Wang3, Cora Woodward2

  • 1Division of Neonatology and Developmental Biology, Department of Pediatrics, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, United States.

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|November 28, 2024
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Summary
This summary is machine-generated.

Diversity-generating retroelements (DGRs) in the gut microbiota rapidly evolve bacterial proteins. These DGRs transfer between species, influencing host-microbe interactions and infant gut colonization.

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Area of Science:

  • Microbiology
  • Evolutionary Biology
  • Genomics

Background:

  • Diversity-generating retroelements (DGRs) are known to accelerate protein evolution.
  • The human gut microbiota has a high density of DGRs, suggesting crucial adaptive roles.
  • Bacteroides species are key members of the human gut microbiota.

Purpose of the Study:

  • To investigate the diversity, activity, and function of DGRs in human-associated Bacteroides species.
  • To understand the mechanisms of DGR horizontal transfer and their impact on protein diversification.
  • To explore the role of DGRs in host-microbe interactions and infant gut colonization.

Main Methods:

  • Bioinformatic identification and analysis of over 1,100 unique DGRs in Bacteroides species.
  • Experimental characterization of DGR activity and horizontal transfer.
  • Competition assays in gnotobiotic mice to assess the adaptive significance of DGR-diversified proteins.
  • Analysis of over 2,700 DGRs across diverse phyla in mother-infant pairs.

Main Results:

  • A subset of Bacteroides DGRs diversifies adhesive components of Type V pili and related proteins.
  • Bacteroides DGRs are horizontally transferred across species, with varying levels of activity.
  • DGRs preferentially alter functional characteristics of ligand-binding residues on adhesive organelles.
  • Specific DGR-driven protein variants are enriched during competition with other commensal bacteria.
  • Bacteroides DGRs are preferentially transferred to vaginally delivered infants and actively diversify.

Conclusions:

  • Bacteroides DGRs play a significant role in adaptive evolution within the human gut.
  • Horizontal transfer and targeted diversification by DGRs contribute to shaping host-associated microbial communities.
  • DGRs represent a key mechanism of stochastic, targeted genome plasticity in microbial evolution.