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Metagenomic targets of balancing selection in the human gut
  • Andrew H. Moeller
Andrew H. Moeller
Cornell University

Corresponding Author:[email protected]

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Bacteria in the human gut contend with numerous fluctuating environmental variables, including bouts of extreme selective agents like antibiotics. Theory predicts that oscillations in the adaptive landscape can impose balancing selection on bacterial populations, leaving characteristic signatures in the sequence variation of functionally significant genomic loci. Despite their potential importance for gut bacterial adaptation, the metagenomic targets of balancing selection have not been identified. Here, I present population genetic evidence that balancing selection maintains allelic diversity in multidrug efflux pumps of multiple predominant bacterial species in the human gut metagenome. Metagenome wide scans of 566,958 core open reading frames (CORFs) from 287 bacterial species represented by 118,617 metagenome assembled genomes (MAGs) indicated that most CORFs have been conserved by purifying selection. However, dozens of CORFs displayed positive Tajima’s D values that deviated significantly from their species’ genomic backgrounds, indicating the action of balancing selection. The AcrB subunit of a multidrug efflux pump (MEP) in Bacteroides dorei displayed the highest Tajima’s D of any CORF, and AcrB and other MEPs from a diversity of bacterial species were significantly enriched among the CORFs with the highest Tajima’s D values. Crystal structures indicated that the regions under balancing selection bind tetracycline and macrolide antibiotics. Other proteins identified as targets of balancing selection included synthases, hydrolases, and ion transporters. Intriguingly, bacterial species experiencing balancing selection were the most abundant in the human gut based on metagenomic data, further suggesting fitness benefits of the allelic variation identified.
30 Oct 2021Submitted to Molecular Ecology
01 Nov 2021Submission Checks Completed
01 Nov 2021Assigned to Editor
17 Nov 2021Reviewer(s) Assigned
19 Jan 2022Review(s) Completed, Editorial Evaluation Pending
28 Jan 2022Editorial Decision: Revise Minor
07 Feb 2022Review(s) Completed, Editorial Evaluation Pending
07 Feb 20221st Revision Received
14 Feb 2022Reviewer(s) Assigned
10 Mar 2022Editorial Decision: Revise Minor
12 Mar 2022Review(s) Completed, Editorial Evaluation Pending
12 Mar 20222nd Revision Received
16 Mar 2022Reviewer(s) Assigned
12 Apr 2022Editorial Decision: Accept