Glycoprotein Hormones and Their Receptors Emerged at the Origin of Metazoans
Bibliographic record
Abstract
The cystine knot growth factor (CKGF) superfamily includes important secreted developmental regulators, including the families of transforming growth factor beta, nerve growth factor, platelet-derived growth factor, and the glycoprotein hormones (GPHs). The evolutionary origin of the GPHs and the related invertebrate bursicon hormone, and their characteristic receptors, contributes to an understanding of the endocrine system in metazoans. Using a sensitive search method with hidden Markov models, we identified homologs of the hormones and receptors, along with the closely related bone morphogenetic protein (BMP) antagonists in basal metazoans. In sponges and a comb jelly, cystine knot hormones (CKHs) with mixed features of GPHs, bursicon, and BMP antagonists were identified using primary sequence and phylogenetic analysis. Also, we identified potential receptors for these CKHs, leucine-rich repeat-containing G protein-coupled receptors (LGRs), in the same species. Cnidarians, such as the sea anemone, coral, and hydra, diverged later in metazoan evolution and appear to have duplicated and differentiated CKH-like peptides resulting in bursicon/GPH-like peptides and several BMP antagonists: Gremlin (Grem), sclerostin domain containing (SOSD), neuroblastoma suppressor of tumorigenicity 1 (NBL1), and Norrie disease protein. An expanded cnidarian LGR group also evolved, including receptors for GPH and bursicon. With the appearance of bilaterians, a separate GPH (thyrostimulin) along with bursicon and BMP antagonists were present. Synteny indicates that the GPHs, Grem, and SOSD have been maintained in a common gene neighborhood throughout much of metazoan evolution. The stable and highly conserved CKGFs are not identified in nonmetazoan organisms but are established with their receptors in the basal metazoans, becoming critical to growth, development, and regulation in all animals.
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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 | 0.000 | 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 | 0.001 | 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".