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Gene-specific selective sweeps are pervasive across human gut microbiomes

Wolff, Richard1; Garud, Nandita1

Published Oct 21, 2025 on Dryad. https://doi.org/10.5061/dryad.9ghx3ffx4

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Abstract

The human gut microbiome is composed of a highly diverse consortia of species that are continually evolving within and across hosts. The ability to identify adaptations common to many human gut microbiomes would not only reveal shared selection pressures across hosts, but also key drivers of functional differentiation of the microbiome that may affect community structure and host traits. However, the extent to which adaptations have spread across human gut microbiomes is relatively unknown. Here, we develop a novel selection scan statistic named the integrated Linkage Disequilibrium Score (iLDS) that can detect sweeps of adaptive alleles spreading across host microbiomes via migration and horizontal gene transfer. Specifically, iLDS leverages signals of hitchhiking of deleterious variants with a beneficial variant. Application of the statistic to ~30 of the most prevalent commensal gut species from 24 human populations around the world revealed more than 300 selective sweeps across species. We find an enrichment for selective sweeps at loci involved in carbohydrate metabolism, indicative of adaptation to host diet, and we find that the targets of selection significantly differ between industrialized and non-industrialized populations. One of these sweeps is at a locus known to be involved in the metabolism of maltodextrin, a synthetic starch that has recently become a widespread component of industrialized diets. In summary, our results indicate that recombination between strains fuels pervasive adaptive evolution among human gut commensal bacteria, and strongly implicate host diet and lifestyle as a critical selection pressures.