Developing a Catalytically Functional Ribonucleotide Reductase for Neurospora Crassa that Lacks Heterokaryon Incompatibility Activity
Bibliographic record
Abstract
We are exploring the structure-function relationship of proteins that govern nonself recognition in the filamentous fungus Neurospora crassa.Heterokaryon incompatibility (HI) is a form of nonself recognition in fungi that prevents the proliferation of heterokaryons -cells that contain genetically dissimilar nuclei.In N. crassa HI is governed by het loci, one of which, het-6, comprises two tightly linked incompatibility genes called un-24 and het-6 that function together as a supergene complex.Each gene exists as one of two allelic variants, either Oak Ridge (OR) or Panama (PA), and only two possible haplotypes occur in nature: un-24 OR -het-6 OR or un-24 PA -het-6 PA .The het-6 gene encodes a HET-domain protein with no known function outside of incompatibility whereas un-24 encodes incompatibility function and the large subunit of ribonucleotide reductase (RNR).RNR is an enzyme that is essential for the conversion of ribonucleotides to deoxyribonucleotides, and thus is crucial for DNA synthesis and repair.The OR and PA allelic forms of UN-24 are nearly identical but differ significantly in the final ~60 residues of their C-termini, suggesting that incompatibility activity and specificity are encoded within this variable region.In this study we identify a single glutamic acid residue within the C-terminus of UN-24 OR that governs incompatibility specificity.In addition, by changing this glutamic acid to leucine we produced an enzymatically functional RNR in N. crassa that lacks incompatibility activity (UN-24 0 ).Prior to this, any perturbation of un-24 resulted in a loss of catalytic activity and cell death, creating a barrier to the study of possible het-6 allelic interactions.Using this un-24 0 strain, we provide insight into the role that HET-6 proteins play in nonself recognition.
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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 | 0.000 | 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 | 0.001 | 0.000 |
| 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 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".