Evolutionary constraints on positional sequence, collective properties and sequence style of tropoelastin dictated by fundamental requirements for formation and function of the extracellular elastic matrix
Bibliographic record
Abstract
• a comprehensive, well-curated database of amniote tropoelastin sequences was created. • conservation of both linear sequence and collective properties of tropoelastins was demonstrated. • characteristics fundamental for tropoelastin assembly and function were identified. • regions of weak sequence conservation retained a sequence style based on hPGhGG repeats. • data suggest a rich source of evolutionarily permitted modulations of elastic matrix properties. Elastin is the extracellular matrix protein responsible for properties of extension and energy-efficient elastic recoil in large blood vessels, lung parenchyma and other vertebrate tissues. Monomeric tropoelastin assembles by phase separation into an extended polymeric matrix covalently cross-linked through lysine residues, producing a robust biomaterial able to withstand hundreds of millions of cycles of extension and recoil. Elastin functions as an entropic elastomer, whose properties are the direct result of the inability of the protein to fold into a fixed, stable structure. Most investigations of how the unusual properties of polymeric elastin arise from the sequence of tropoelastin have utilized molecular biological/biophysical methodologies. This study takes an alternative approach, using a comprehensive, well-curated database of Amniote tropoelastin sequences to identify characteristics conserved through >300 million years of evolution. Conserved characteristics included preservation of not only regions of positional sequence but also collective or compositional characteristics derived from but not strictly dependent on positional sequence. A plausible overall consensus sequence for Amniote tropoelastins allowed quantification of residue-by-residue, domain-by-domain and region-by-region levels of sequence conservation. Regions of low positional sequence conservation nevertheless maintained a recognizable sequence style characterized by tandem repeats and partial repeats of short, non-polar motifs. Motif analysis suggested hPGhGG, with numerous insertions and deletions, as the underlying repeating unit in all Amniote tropoelastins. The data identify significant evolutionary constraints dictated by fundamental requirements for formation and functionality of the extracellular elastin matrix, and suggest a rich source of evolutionarily permitted opportunities for modulating properties to meet specific species requirements.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".