Rapid genetic diversification of <i>Bacteroides thetaiotaomicron</i> in mono-associated mice revealed through deep population-level sequencing
Bibliographic record
Abstract
Abstract Bacteria often feature short generation times and large populations, thereby allowing them to quickly evolve and adapt to new environments. Although it is known that gut bacteria can evolve on relatively short time scales, the extent of genetic diversification of bacteria in the gut environment remains underexplored. Here, we characterize the genetic diversification of the gut commensal Bacteroides thetaiotaomicron during 28 days of colonization of germ-free mice using deep shotgun sequencing as well as genome analysis of evolved isolates. We detect thousands of genetic polymorphisms as early as three days post inoculation and observe highly dynamic genetic diversity in the distal gut. We identify multiple haplotypes of a phase-variable polysaccharide utilization locus ( BT2260 - BT2268 ) and propose that phase variation may be an important mechanism for diversification and adaptation in the gut. In addition, we find evidence that hybrid two-component system ( HTCS) regulators are mutational hotspots. We identify multiple persistent and parallelly evolved genetic polymorphisms in genes, including the TonB-dependent transporter BT0867 - a homolog of BF3581 from the commensal colonization factor ( ccf ) in B. fragilis . Lastly, we find that the small intestine accumulated approximately 20 times more polymorphisms compared to the large intestine, highlighting overall the importance of studying spatiotemporal distribution of genetic variants. These results underscore the prevalence of rapid genetic diversification of gut bacteria, which may have important implications for adaptation as well as interactions in the microbiome and with the host. Importance Studying the within-host evolution of gut commensals is an essential step for understanding the role of microbiome in health and disease. It can provide insights into the mechanisms underlying the development of various gastrointestinal disorders, metabolic conditions, autoimmune diseases, and other health disorders. Additionally, this kind of research can further drive the development of personalized therapies, such as strain-level or gene specific interventions for improving health outcomes. Here, we report extensive genetic variation within days upon colonization of mice with B. thetaiotaomicron and identify genes that accumulate persistent and highly prevalent genetic polymorphisms across a mouse population. We also detect several haplotypes in phase-variable loci. Altogether, our findings underscore the rapid pace of genetic diversification and phase variation upon colonization of the gut environment.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".