Comparative Evolutionary Genomics Reveals Genetic Diversity and Differentiation in Bacteroides fragilis

Bacteroides fragilis is the pathogenic anaerobe most commonly isolated from intra-abdominal infections, abscesses, and blood. Despite its clinical importance, research on its pan-genome-scale evolution is still limited.

Herein, we analyzed the pan-genome architecture of 374 B. fragilis strains to explore their intra-species genomic diversity and evolutionary patterns.

Our analysis revealed an open pan-genome with a high proportion of accessory genomes, indicating high genetic variability. Accessory genome genes were substantially enriched in the functions of "Replication, Recombination, and Repair" suggesting their roles in gene transfer and divergence. Phylogenomic analysis divided B. fragilis into two distinct clades: divisions I and II, differing in gene content, antimicrobial resistance genes, and mobile genetic elements. Division II revealed higher Tajima's D values, suggesting that it separated after B. fragilis's recent species diversification. The extreme shift in the distribution of gene-wise Hudson's fixation index (Fst) values for each division suggested that several genes are highly differentiated or evolved between the two clades. Average nucleotide identity and 16S rRNA analyses showed that B. fragilis division II represents a distinct species, Bacteroides hominis. Additionally, a considerable depletion of recombination in genes with Fst values > 0.99 was noted, suggesting that the highest Fst genes with little recombination are the basis for differentiation between divisions.

Overall, this study enhances the understanding of B. fragilis's genomic diversity, evolutionary dynamics, and potential role in pathogenesis, shedding light on its adaptation and diversification.