Stochastic offspring distributions amplify selection bias in mutation accumulation experiments
Bibliographic record
Abstract
Mutation accumulation (MA) experiments play an important role in understanding evolution. For microbial populations, such experiments often involve periods of population growth, such that a single individual can make a visible colony, followed by severe bottlenecks. Previous work has quantified the effect of positive and negative selection on MA experiments, demonstrating for example that with 20 generations of growth between bottlenecks, big-benefit mutations can be over-represented by a factor of five or more (Wahl and Agashe, 2022). This previous work assumed a deterministic model for population growth. We now develop a fully stochastic model, including realistic offspring distributions that incorporate genetic drift and allow for the loss of rare lineages. We demonstrate that when stochastic offspring distributions are considered, selection bias is even stronger than previously predicted. We describe several analytical and numerical methods that offer an accurate correction for the effects of selection on the observed distribution of fitness effects, describe the practical considerations in implementing each method, and demonstrate the use of this correction on simulated MA data. • We quantify bias due to positive and negative selection in mutation accumulation experiments, using realistic offspring distributions. • When drift is included, selection bias is even stronger than previously predicted. • We provide analytical and numerical methods to correct MA data for selection.
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How this classification was reachedexpand
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".