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

Abstract

Despite the importance of gut commensal microbiota to human health, there is little knowledge about their evolutionary histories, including their population demographic histories and their distributions of fitness effects (DFE) of new mutations. Here, we infer the demographic histories and DFEs of 27 of the most highly prevalent and abundant commensal gut microbial species in North Americans over timescales exceeding human generations using a collection of lineages inferred from a panel of healthy hosts. We find overall reductions in genetic variation among commensal gut microbes sampled from a Western population relative to an African rural population. Additionally, some species in North American microbiomes display contractions in population size and others expansions, potentially occurring at several key historical moments in human history. DFEs across species vary from highly to mildly deleterious, with accessory genes experiencing more drift compared to core genes. Within genera, DFEs tend to be more congruent, reflective of underlying phylogenetic relationships. Taken together, these findings suggest that human commensal gut microbes have distinct evolutionary histories, possibly reflecting the unique roles of individual members of the microbiome.

Linkage equilibrium between rare mutations

“…Since the typical SNV in E. rectale has a frequency < 1%, these results indicate that the vast majority of SNVs have not yet reached linkage equilibrium, even though the genome-wide values of LD are low (Garud et al, 2019). This observation has important implications for the application of demographic inference methods like ∂a∂i (Gutenkunst et al, 2009;Kim et al, 2017;Mah et al, 2023), which assume that most variants are in linkage equilibrium with each other.…”

“…One important limitation is the assumption of a panmictic population with a constant size. In reality, host-associated organisms like gut bacteria can exhibit complex population structures that depend on their history of dispersal and co-diversification with their hosts (Falush et al, 2003;Mah et al, 2023;Suzuki et al, 2022). Another crucial assumption is the absence of positive selection and hitchhiking of linked neutral loci, which are thought to play an important role in shaping the genetic diversity of natural bacterial populations (Birzu et al, 2023;Liu and Good, 2024;Wolff and Garud, 2023).…”

Tangled genetic relationships within theFusobacteriumgenus

“…Whereas this limits the possibility to perform more detailed analysis of genetic diversity in fusobacteria, the inability to control for external variables might also introduce unrecognized biases. For instance, individual bacterial species were shown to be more genetically diverse among African than non-African human hosts 26,[44][45][46][47] . The unequal representation of genomes from different geographic areas in different species might thus affect our measures of nucleotide diversity.…”

Pervasive selective sweeps across human gut microbiomes

“…Indeed, absent purifying selection, iLDS will fail to detect even the very strongest sweeps. However, we note that purifying selection is a pervasive feature of bacterial genomes [1, 55, 56, 57, 58], and it seems unlikely that there would be large genomic regions devoid of variants that are under purifying selection.…”