DOI: 10.5061/dryad.9ghx3ffx4
title: Gene-specific selective sweeps are pervasive across human gut microbiomes

description: 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.
description: # Gene-specific selective sweeps are pervasive across human gut
 microbiomes Dataset DOI:
 [10.5061/dryad.9ghx3ffx4](https://doi.org/10.5061/dryad.9ghx3ffx4) ##
 Description of the data and file structure All underlying data used in
 this paper is publicly available.  ### Files and variables Note: For a
 complete description of iDLS output variables, see the [Output section of
 the associated Github
 repo.](https://github.com/garudlab/iLDS/tree/main/iLDS#output) #### File:
 TableS4.txt **Description:** **contains all sweeps detected in all
 populations analyzed (QP, UHGG, Drosophila)** ##### Variables * Gene: the
 gene the variant lies in * Contig: the contig the variant lies on (in the
 case of peaks for *Drosophila melanogaster,* this is the chromosome) * SNV
 position (contig): the position of the central intermediate-frequency
 non-synonymous SNP in the analysis window with the highest iLDS value
 along the given contig * Species: Name of the species * Peak number: the
 unique peak to which the variant belongs (peaks are numbered from left to
 right for each species) * Gene product: the gene protein product *
 iLDS: value of iLDS for the variant * Country: For UHGG and Drosophila,
 country where scan was run * Data type: the dataset the scan was performed
 on (quasi-phased metagenomes, UHGG, or Drosophila) * COG: Cluster of
 Orthologous Genes category * EC: Enzyme Commission number of the gene ####
 File: all_QP_scans.zip **Description:** complete iLDS output files for
 each of the 32 QP species.  #### File: cdiff_scan_comparison.zip
 **Description:** iLDS output files as well as output files for iHS,
 Tajima's D, and dN/dS calculations in Extended Data Figure 2.  ####
 File: fig2.zip **Description:** Genomewide decay of LD at synonymous and
 non-synonymous sites for the species *R. bromii* and *P.
 copri.* AUC(r^2^~N~ - r^2^~S~) for all quasi-phased (QP) species. * *R.
 bromii*: R_bromii_ld_decay.txt * *P. copri*: P_copri_ld_decay.txt *
 AUC(r^2^~N~ - r^2^~S~): AUC.txt #### File: fig3.zip **Description:** iLDS
 scans for the species *C. difficile*, *E. siraeum*, and *R. bromii*.
 Number of sweeps for each QP species.  * *C. difficile*:
 cdiff_full_scan.txt * *E.
 siraeum*: Eubacterium_siraeum_57634_full_scan.txt * *R.
 bromii*: rbromii_full_scan.txt * Number sweeps: num_peaks.txt **Note**:
 The iLDS output files (..._full_scan.txt) contain the contains raw output
 files of iLDS. For a complete description of the meanings of each column,
 see the [Output section of the associated Github
 repo.](https://github.com/garudlab/iLDS/tree/main/iLDS#output) #### File:
 fig4.zip **Description:** complete iLDS output files for *R. bromii* in 16
 populations across the world (UHGG). Includes both the Main Text scans
 (Fig 4) as well as the remainder of the scans available in Extended Data
 Figure  8. #### File: tract_length_parameters.txt
 **Description:** detected tract length (*l~r~*) and decay distance
 (*l~DD~*) for each QP species ##### Variables * tract_length: *l~r~* *
 decay_points: *l~DD~* ## Code/software All code necessary to process
 underlying short read data, annotate genomes, measure LD, calculate iLDS,
 perform other analyses, and generate figures can be found in [the
 accompanying GitHub repo for this
 project](https://github.com/garudlab/iLDS/tree/main) as well as in its
 [Zenodo](https://zenodo.org/records/17260630).  ## Access information *
 Shotgun metagenomic samples for the QP analyses was derived from the
 following sources: * 250 individuals from Lloyd-Price *et al.* (2017)
 (accession numbers PRJNA48479 and PRJNA275349) * 250 individuals  from Xie
 *et al.* (2016) (accession number PRJEB9576) * 185 individuals from Qin
 *et al.* (2012) (accession number PRJNA422434) * 8 individuals from
 Korpela et al. (2018) (accession number PRJEB24041) * Alignments of MAGs
 and isolates and accompanying data files from UHGG (Almeida *et al.* 2019)
 were downloaded from
 [MGnify](https://ftp.ebi.ac.uk/pub/databases/metagenomics/mgnify_genomes/human-gut/v1.0/). * Finally, for *Drosophila melanogaster* analyses, we used publicly available Drosophila Genome Nexus data set (Lack *et al.* 2015). These include 205 DGRP strains from Raleigh, North Carolina and 197 DPGP3 strains from Zambia. These data can be downloaded at [www.johnpool.net](http://www.johnpool.net/).