Gain- and loss-of-function alleles within signaling pathways lead to phenotypic diversity among individuals
Bibliographic record
Abstract
) and found variation in the activity of MAPK signaling pathways as a contributing mechanism. To uncover the genetic basis of this mechanism, we identified 1957 SNPs in 62 candidate genes encoding signaling proteins from a MAPK signaling module within a large collection of yeast (>1500 individuals). Follow-up testing identified functionally relevant variants in key signaling proteins. Loss-of-function (LOF) alleles in a PAK kinase impacted protein stability and pathway specificity decreasing filamentous growth and mating phenotypes. In contrast, gain-of-function (GOF) alleles in G-proteins that were hyperactivating induced filamentous growth. Similar amino acid substitutions in G-proteins were identified in metazoans that in some cases were fixed in multicellular lineages including humans, suggesting hyperactivating GOF alleles may play roles in generating phenotypic diversity across eukaryotes. A mucin signaler that regulates MAPK activity was also found to contain a prevalance of presumed GOF alleles amoung individuals based on changes in mucin repeat numbers. Thus, genetic variation in signaling pathways may act as a reservoir for generating phenotypic diversity across eukaryotes.
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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".