The Nature of Variation in Mutational Properties: Context-dependent Changes in Mutation Rates and Mutational Fitness Effects
Bibliographic record
Abstract
Evaluating the evolutionary role of mutations depends on an understanding of their major properties, including their rate of origin, U, and the distribution of their fitness effects, f(s). While substantial effort has been put into measuring these properties, most studies have only examined their distributions in a single context. In nature, spontaneous mutations are likely to experience heterogeneity in genetic and environmental context, and this could lead to variation in both U and f(s). My thesis investigates the changes in U and f(s) with different genetic and environmental factors in Drosophila melanogaster, in order to elucidate the nature of context-associated variation in mutational properties. Examination of condition-dependent variation in DNA repair showed that high and low conditioned individuals differ in the use of alternative repair pathways. This could ultimately lead to variance in their heritable mutation rates. However, the assumption that condition dependence in repair arises solely due to a presumed trade-off between accuracy and the energetic costs associated with different repair pathways is too simplistic. Instead, physiological considerations appear to mediate condition-dependent changes in DNA repair. Measurements of selection on individual mutations across different genetic and environment contexts showed that context-associated changes in mutational fitness effects are common. I found that heterogeneity in fitness effects across different environments result in changes to the overall mean and variance of f(s). This does not, however, seem attributable to the degree of ‘adaptedness’ of a population to a particular environment (a prediction generated by previous theoretical analysis). On the other hand, f(s) appears to be relatively robust to differences among genotypes, with epistasis averaging close to zero. This finding suggests that genetic and environmental perturbations may affect mutations differently. Overall, my thesis represents the most rigorous empirical investigation to date of the conceptual and theoretical predictions regarding the nature of context-dependent heterogeneity in U and f(s) for multicellular eukaryotes.
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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 | 0.002 | 0.008 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 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".