A Hadza-enriched Prevotella/Segatella xyloglucanase shows sequence conservation and functional specialization

Bacteria can adapt to their environment through changes in their genetic material. A large proportion of gut bacteria are shaped by host-specific diet, including complex carbohydrates. The bacterial abundance, genetic content within the same bacterial species, and sequence-level variation in genes encoding similar carbohydrate-processing enzymes may therefore vary across hosts with different diets. We previously found that the abundance of diet-degrading genes varies between hominid host populations from Tanzania. We therefore hypothesized that, in addition to these abundance differences, selective pressure could act on individual gene sequences. Here, we investigated Tanzanian hominid gut microbiome differences at the taxonomic, genetic, structural, and functional levels. We analyzed 15,146 metagenome-assembled genomes (MAGs) spanning 1563 species and identified one species with striking host-associated separation. In particular, sequence variation in a xyloglucanase-encoding gene correlated strongly with the host population. This gene was highly conserved in the Hadza population, suggesting a role in the processing of diet-associated polysaccharides. Sequence differences and structural modeling revealed amino acid substitutions near the catalytic site, and biochemical assays using xyloglucan showed that representative variants differed in activity under identical assay conditions. Collectively, our findings suggest that host lifestyle and diet contribute to population-associated sequence variation in genes encoding enzymes involved in degrading polysaccharides.