Evolution of hypoxia‐responsive cytochrome c oxidase genes
Bibliographic record
Abstract
Among the mechanisms that fine‐tune cytochrome c oxidase (COX) levels/activities is an oxygen‐dependent switch of paralogs for subunit 4. COX4‐1 is constitutively expressed in most tissues; COX4‐2 predominates in brain and lung and is induced by hypoxia in other tissues. Though there is considerable evidence that this isoform switch has advantages in COX regulation under energetic stress, the evolutionary origins of the adaptation are unclear. All vertebrates possess single gene copies of both orthologs, though birds lack a functional COX4‐2 gene. Mammals, amphibians and reptiles display considerable diversity in the distribution, degeneracy and efficacy of canonical hypoxia‐responsive elements (HRE) and oxygen‐responsive elements (ORE). Fish display mammalian‐like tissue expression profiles of COX4‐1 and COX4‐2, but we find no evidence that COX4‐2 is hypoxia responsive; fish and fish cells do not alter COX4‐2 expression under hypoxia or anoxia, and their proximal promoters lack HRE or ORE elements homologous to the human gene. These studies suggest that the COX4‐2 paralog is near ubiquitous in vertebrates, but its oxygen responsiveness is perhaps limited to mammals. Even in mammals, its oxygen sensitivity differs among tissues and between cancer lines. Funded by NSERC Canada.
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".