The properties of spontaneous mutations in the opportunistic pathogen Pseudomonas aeruginosa
Why this work is in the frame
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Bibliographic record
Abstract
BACKGROUND: Natural genetic variation ultimately arises from the process of mutation. Knowledge of how the raw material for evolution is produced is necessary for a full understanding of several fundamental evolutionary concepts. We performed a mutation accumulation experiment with wild-type and mismatch-repair deficient, mutator lines of the pathogenic bacterium Pseudomonas aeruginosa, and used whole-genome sequencing to reveal the genome-wide rate, spectrum, distribution, leading/lagging bias, and context-dependency of spontaneous mutations. RESULTS: Wild-type base-pair mutation and indel rates were ~10(-10) and ~10(-11) per nucleotide per generation, respectively, and deficiencies in the mismatch-repair system caused rates to increase by over two orders of magnitude. A universal bias towards AT was observed in wild-type lines, but was reversed in mutator lines to a bias towards GC. Biases for which types of mutations occurred during replication of the leading versus lagging strand were detected reciprocally in both replichores. The distribution of mutations along the chromosome was non-random, with peaks near the terminus of replication and at positions intermediate to the replication origin and terminus. A similar distribution bias was observed along the chromosome in natural populations of P. aeruginosa. Site-specific mutation rates were higher when the focal nucleotide was immediately flanked by C:G pairings. CONCLUSIONS: Whole-genome sequencing of mutation accumulation lines allowed the comprehensive identification of mutations and revealed what factors of molecular and genomic architecture affect the mutational process. Our study provides a more complete view of how several mechanisms of mutation, mutation repair, and bias act simultaneously to produce the raw material for evolution.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it