Paralog interference preserves genetic redundancy
Why this work is in the frame
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Bibliographic record
Abstract
Models of gene duplication often assume that loss-of-function mutations neutrally promote the return to the ancestral singleton state. They thus ignore the potential functional interference between duplicated proteins stemming from their physical interactions. Here, we show that for heteromerizing paralogs, such interference potentiates negative selection on loss-of-function mutations. This effect maintains genetic redundancy over longer timescales depending on the rate and severity of loss-of-function mutations. We experimentally estimate that around 6% of deleterious substitutions for a representative tetrameric protein interfere with a second copy. Interfering mutations typically disrupt either catalysis or the final step of protein complex assembly, with varying degrees of severity. Our work shows that paralog interference potentiates the negative effects of loss-of-function mutations, contributing to the preservation of genetic redundancy.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.000 | 0.001 |
| 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