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

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 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.

Inference of the demographic histories and selective effects of human gut commensal microbiota over the course of human history

“…By contrast, the differences in the DFEs for core vs accessory genes are less likely due to differences in s and instead due to differences in N Anc . In support of this, accessory genes have lower N Anc than core genes ( Figure S13 ), and have elevated levels of pN/pS (N’Guessan et al 2021, Genome Biology and Evolution; Cooper et al 2010, PLoS Computational Biology; Olm et al 2021, Nature Biotechnology), suggesting that weakly deleterious mutations can drift to higher frequency due to the smaller effective population size.…”

A global survey of prokaryotic genomes reveals the eco-evolutionary pressures driving horizontal gene transfer

“…Multiple studies have considered the function of transferred genes 9 , 13 , 15 , 18 , 27 – 34 , which, in the context of very recent transfers, has been shown to be predictive of HGT events 15 . To explore further, we divided our landscape of detected transfer events into bins based on species and gene distance and performed functional enrichment analysis for each bin using the Clusters of Orthologous Genes (COG) categories from eggNOG 35 (Fig.…”

Insights into early evolutionary adaptations of the Akkermansia genus to the vertebrate gut

“…These two categories are commonly found to unfollow the neutral theory of molecular evolution in bacterial genomes; for example, some genes related to CRISPR are in a constant arms race, which involves a process of coevolution between bacteriophages and bacteria interaction ( Takeuchi et al, 2012 ). In the same way, genes in a COG category like N (including genes related to transfer events between bacterial cells) are under the effect of purifying selection, which involves a tendency to molecular change at the gene level ( N’Guessan et al, 2021 ).…”