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Cavanaugh, C. M.

Publications and source records attributed to Cavanaugh, C. M..

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Gene- and genome-centric dynamics shape the diversity of oral bacterial populations

Two major viewpoints have been put forward for how microbes adapt to a niche, differing in whether adaptation is driven principally by gene-centric or genome-centric processes. Longitudinal sampling at microbially-relevant timescales, i.e., days to weeks, is critical for distinguishing these mechanisms. Because of its significance for both microbial ecology and human health and its accessibility and high level of curation, we used the oral microbiota to evaluate evolutionary mechanisms. Metagenomes were generated by shotgun sequencing of total community DNA from the healthy tongues of 17 volunteers at four to seven timepoints obtained over intervals of days to weeks. We obtained 390 high-quality metagenome-assembled genomes (MAGs) defining population genomes from 55 genera, the majority of which were temporally stable at the MAG level. Decomposing MAG-defined populations by single nucleotide variant frequencies revealed MAGs were composed of up to 5 haplotypes, putatively distinct strain- or subpopulation-level genotypes. Most haplotypes were stable over time, yet we found examples of individual haplotypes sweeping from low abundance to dominance in a population over a period of days, a pattern suggestive of genome-centric adaptation. At the gene level, the vast majority of genes in each MAG were tightly linked over the two-week sampling window based on their frequency in the metagenomes of different mouths. The few genes that changed in abundance independently from nearby genes did not change in a directional manner, nor did nonsynonymous codon variants within such genes. Altogether, these observations characterize the intrapopulation genomic dynamics of the oral microbiota at microbially-relevant timescales. Our results demonstrate that both gene- and genome-wide sweeps occur on daily timescales but likely with different ecological ramifications. We infer that genome-wide selection of ecotypes is the dominant mode of adaptation in the oral populations, with short-term changes in gene frequency also occurring.

microbiology

Metapangenomics of the oral microbiome provides insights into habitat adaptation and cultivar diversity

BackgroundThe 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. ResultsHere, 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 not only limitations in the ability of cultivated organisms to represent populations in their native environment, but also specifically which cultivar gene sequences were absent or ubiquitous. ConclusionsOur 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.

microbiology