Comparative genomics of novel Bacteroides acidifaciens isolates reveals candidates for adaptation to host subspecies in house mice

The breadth of phenotypes influenced by the gut microbiome in multicellular hosts has attracted the keen and renewed interest of evolutionary biologists. Comparative studies suggest that coevolutionary processes may occur as hosts and their associated microbes (i.e., holobionts) diverge. The majority of studies to date however lack information beyond that of 16S rRNA gene profiling, and thus fail to capture potential underlying genomic changes among microbes. In this study, we conducted a comparative genomic analysis of 19 newly sampled Bacteroides acidifaciens isolates derived from the eastern and western house mouse subspecies, Mus musculus musculus and M. m. domesticus . Through a panel of genome-wide association (GWAS) analyses applied to pangenomic content, structural gene rearrangements, and SNPs, we reveal several candidates for adaptation to the host subspecies environment. The proportion of significant loci in each respective category is small, indicating low levels of differentiation according host subspecies. However, consistent signal is observed for genes involved in processes such as carbohydrate acquisition/utilization (SusD/RagB, amyA and amyS ) and de novo purine nucleotide biosynthesis ( purD ), which serve as promising candidates for future experimental investigation in the house mouse as a model of holobiont evolution.