Ancient origin of the furin sequence in the wolf F8 gene
Bibliographic record
Abstract
Background: Our previous characterization of canine coagulation factor VIII (FVIII) in the naturally occurring hemophilia A (HA) dog models provided insight into the evolution of the FVIII protein. We noted a unique sequence (H1645) in the R-X-X-R furin-recognition motif within the B domain of canine FVIII that was distinct from the sequence (R1645) in humans and other model organism species, including mice, rats, pigs, and sheep. R1645 was associated with lower secretion and biological activity, which can be improved with the canine H1645 sequence. Aim: Herein, we sought to determine the evolutionary origin of the canine H1645. Methods: ), in several free-range animals from diverse geographic locations and compared it to several breeds of domestic dogs. We also compared our sequences to publicly available reference sequences for other members of the class Mammalia, order Carnivora, and suborder Caniformia. Results: 19 X chromosomes from 12 gray wolves, at least 20 X chromosomes from 14 coyotes, and at least 12 X chromosomes from 12 domestic dogs of at least 10 distinct breeds all had the canine H1645 variant. Other members of the order Carnivora and suborder Caniformia, whose sequences are publicly available, had the R1645 sequence. Conclusion: Our results suggest that the H1645 variant in the furin-consensus sequence was likely derived after the infraorders Cynoidea and Arctoidea diverged but before the separation of the gray wolf and coyote and persists through the domestic dog.
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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 | 0.001 | 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 | 0.000 |
| 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".