Metagenomic targets of balancing selection in the human gut
Andrew H. Moeller1,2
1Department of Ecology and Evolutionary Biology,
Cornell University, Ithaca, NY 14805
2corresponding author:
andrew.moeller@cornell.edu
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) inBacteroides 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.