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

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Area of Science:

  • Microbiology
  • Evolutionary Biology
  • Genomics

Background:

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

Purpose of the Study:

  • To identify and characterize DGRs in human-associated Bacteroides species.
  • To investigate the function and transfer of these DGRs.
  • To understand the role of DGRs in shaping host-associated microbial communities.

Main Methods:

  • Bioinformatic identification of >1100 distinct DGRs in Bacteroides species.
  • Analysis of DGR activity and targets, including type V pili.
  • Horizontal gene transfer analysis and competition assays in gnotobiotic mice.
  • Comparative analysis of >2700 DGRs across phyla in mother-infant pairs.

Main Results:

  • A subset of Bacteroides DGRs diversifies adhesive proteins of type V pili.
  • Bacteroides DGRs are horizontally transferred across species and exhibit variable activity levels.
  • DGRs preferentially alter ligand-binding residues, and specific sequences are enriched during bacterial competition.
  • Bacteroides DGRs are disproportionately transferred to vaginally delivered infants and actively diversify.

Conclusions:

  • Bacteroides DGRs contribute to microbial adaptation and evolution within the human gut.
  • Horizontal transfer of DGRs, particularly to infants, plays a significant role in shaping the gut microbiome.
  • Targeted genome plasticity via DGRs is a key factor in host-associated microbial community dynamics.