TY - JOUR T1 - Metapangenomics of the oral microbiome provides insights into habitat adaptation and cultivar diversity JF - bioRxiv DO - 10.1101/2020.05.01.072496 SP - 2020.05.01.072496 AU - Daniel R. Utter AU - Gary G. Borisy AU - A. Murat Eren AU - Colleen M. Cavanaugh AU - Jessica L. Mark Welch Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/02/2020.05.01.072496.abstract N2 - Background The increasing availability of microbial genomes and environmental shotgun metagenomes provides unprecedented access to the genomic differences within related bacteria. The human oral microbiome with its diverse habitats and abundant, relatively well-characterized microbial inhabitants presents an opportunity to investigate bacterial population structures at an ecosystem scale.Results Here, we employ a metapangenomic approach that combines public genomes with Human Microbiome Project (HMP) metagenomes to study the diversity of microbial residents of three oral habitats: tongue dorsum, buccal mucosa, and supragingival plaque. For two exemplar taxa, Haemophilus parainfluenzae and the genus Rothia, metapangenomes revealed distinct genomic groups based on shared genome content. H. parainfluenzae genomes separated into three distinct subgroups with differential abundance between oral habitats. Functional enrichment analyses identified an operon encoding oxaloacetate decarboxylase as diagnostic for the tongue-abundant subgroup. For the genus Rothia, grouping by shared genome content recapitulated species-level taxonomy and habitat preferences. However, while most R. mucilaginosa were restricted to the tongue as expected, two genomes represented a cryptic population of R. mucilaginosa in many buccal mucosa samples. For both H. parainfluenzae and the genus Rothia, we identified limitations in the ability of cultivated organisms to represent populations in their native environment, as the environmental distribution of cultivar gene sequences ranged from absent to ubiquitous.Conclusions Our findings provide insights into population structure and biogeography in the mouth and form specific hypotheses about habitat adaptation. These results illustrate the power of combining metagenomes and pangenomes to investigate the ecology and evolution of bacteria across analytical scales.Competing Interest StatementThe authors have declared no competing interest. ER -