Evolution and structural diversification of hyperpolarization-activated cyclic nucleotide-gated channel genes
Why this work is in the frame
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Bibliographic record
Abstract
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are members of the voltage-gated channel superfamily and play a critical role in cellular pace-making. Overall sequence conservation is high throughout the family, and channel functions are similar but not identical. Phylogenetic analyses are imperative to understand how these genes have evolved and to make informed comparisons of HCN structure and function. These have been previously limited, however, by the small number of available sequences, from a minimal number of species unevenly distributed over evolutionary time. We have now identified and annotated 31 novel genes from invertebrates, urochordates, fish, amphibians, birds, and mammals. With increased sequence numbers and a broader species representation, a more precise sequence comparison was performed and an evolutionary history for these genes was constructed. Our data confirm the existence of at least four vertebrate paralogs and suggest that these arose via three duplication and diversification events from a single ancestral gene. Additional lineage-specific duplications appear to have occurred in urochordate and fish genomes. Based on exon boundary conservation and phylogenetic analyses, we hypothesize that mammalian gene structure was established, and duplication events occurred, after the divergence of urochordates and before the divergence of fish from the tetrapod lineage. In addition, we identified highly conserved sequence regions that are likely important for general HCN functions, as well as regions with differences conserved among each of the individual paralogs. The latter may underlie more subtle isoform-specific properties that are otherwise masked by the high identity among mammalian orthologs and/or inaccurate alignments between paralogs.
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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