Pervasive selective sweeps across human gut microbiomes

The human gut microbiome is composed of a highly diverse consortia of species which are continually evolving within and across hosts. The ability to identify adaptations common to many host 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, to date there has not been a systematic scan for adaptations that have spread across host microbiomes. Here, we develop a novel selection scan statistic, named the integrated linkage disequilibrium score (iLDS), that can detect the spread of adaptive haplotypes across host microbiomes via migration and horizontal gene transfer. Specifically, iLDS leverages signals of hitchhiking of deleterious variants with the beneficial variant, a common feature of adaptive evolution. We find that iLDS is capable of detecting simulated and known cases of selection, and moreover is robust to potential confounders that can also elevate LD. Application of the statistic to ∼20 common commensal gut species from a large cohort of healthy, Western adults reveals pervasive spread of selected alleles across human microbiomes mediated by horizontal gene transfer. Among the candidate selective sweeps recovered by iLDS is an enrichment for genes involved in the metabolism of maltodextrin, a synthetic starch that has recently become a widespread component of Western diets. In summary, we demonstrate that selective sweeps across host microbiomes are a common feature of the evolution of the human gut microbiome.

Link to OA paper: https://www.biorxiv.org/content/10.1101/2023.12.22.573162v1