Mobile Gene Sequence Evolution within Individual Human Gut Microbiomes Is Better Explained by Gene-Specific Than Host-Specific Selective Pressures

Abstract

Abstract Pangenomes—the cumulative set of genes encoded by a population or species—arise from the interplay of horizontal gene transfer, drift, and selection. The balance of these forces in shaping pangenomes has been debated, and studies to date focused on ancient evolutionary time scales have suggested that pangenomes generally confer niche adaptation to their bacterial hosts. To shed light on pangenome evolution on shorter evolutionary time scales, we inferred the selective pressures acting on mobile genes within individual human microbiomes from 176 Fiji islanders. We mapped metagenomic sequence reads to a set of known mobile genes to identify single nucleotide variants (SNVs) and calculated population genetic metrics to infer deviations from a neutral evolutionary model. We found that mobile gene sequence evolution varied more by gene family than by human social attributes, such as household or village. Patterns of mobile gene sequence evolution could be qualitatively recapitulated with a simple evolutionary simulation without the need to invoke the adaptive value of mobile genes to either bacterial or human hosts. These results stand in contrast with the apparent adaptive value of pangenomes over longer evolutionary time scales. In general, the most highly mobile genes (i.e., those present in more distinct bacterial host genomes) tend to have higher metagenomic read coverage and an excess of low-frequency SNVs, consistent with their rapid spread across multiple bacterial species in the gut. However, a subset of mobile genes—including those involved in defense mechanisms and secondary metabolism—showed a contrasting signature of intermediate-frequency SNVs, indicating species-specific selective pressures or negative frequency-dependent selection on these genes. Together, our evolutionary models and population genetic data show that gene-specific selective pressures predominate over human or bacterial host-specific pressures during the relatively short time scales of a human lifetime.