Toward a Better Understanding of G4 Evolution in the 3 Living Kingdoms
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Bibliographic record
Abstract
Background: G-quadruplexes (G4s) are secondary structures in DNA and RNA that impact various cellular processes, such as transcription, splicing, and translation. Due to their numerous functions, G4s are involved in many diseases, making their study important. Yet, G4s evolution remains largely unknown, due to their low sequence similarity and the poor quality of their sequence alignments across several species. To address this, we designed a strategy that avoids direct G4s alignment to study G4s evolution in the 3 species kingdoms. We also explored the coevolution between RBPs and G4s. Methods: We retrieved one-to-one orthologous genes from the Ensembl Compara database and computed groups of one-to-one orthologous genes. For each group, we aligned gene sequences and identified G4 families as groups of overlapping G4s in the alignment. We analyzed these G4 families using Count, a tool to infer feature evolution into a gene or a species tree. Additionally, we utilized these G4 families to predict G4s by homology. To establish a control dataset, we performed mono-, di- and tri-nucleotide shuffling. Results: Only a few conserved G4s occur among all living kingdoms. In eukaryotes, G4s exhibit slight conservation among vertebrates, and few are conserved between plants. In archaea and bacteria, at most, only 2 G4s are common. The G4 homology-based prediction increases the number of conserved G4s in common ancestors. The coevolution between RNA-binding proteins and G4s was investigated and revealed a modest impact of RNA-binding proteins evolution on G4 evolution. However, the details of this relationship remain unclear. Conclusion: Even if G4 evolution still eludes us, the present study provides key information to compute groups of homologous G4 and to reveal the evolution history of G4 families.
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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 | 0.000 |
| 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 it