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
Abstract Elastin is an unusual extracellular matrix protein responsible for the properties of extension and energy-efficient elastic recoil of large blood vessels, heart valves, lung parenchyma and many other vertebrate tissues requiring such resilience. Polymeric elastin is assembled from monomeric tropoelastin by a process involving liquid-liquid phase separation, followed by maturation into an extended elastic matrix, covalently cross-linked through the side chains of lysine residues in the protein and producing a robust biomaterial with the structural integrity to withstand hundreds of millions of cycles of extension and recoil without mechanical failure. 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. Previous investigations of how the unusual properties of polymeric elastin arise from the sequence of tropoelastin have depended primarily on modeling using molecular biological and biophysical methodologies. This study takes a unique alternative approach, using a well-curated database of tropoelastin sequences from more than 80 representative species of Amniotes to identify characteristics that are conserved over more than 300 million years of evolution in order to provide assembly and conformational flexibility requirements of elastins. Conserved characteristics included preservation not only of regions of linear or positional sequence, but also of collective or compositional characteristics, derived from the sequence 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, identifying distinct regions of high and low positional sequence conservation. Regions of low positional sequence conservation nevertheless maintained a recognizable, low complexity sequence style characterized by tandem repeats and partial repeats of short, non-polar motifs. Analysis of these motifs indicated hPGhGG, with numerous mutations, insertions and deletions, as the underlying repeating unit in all Amniote tropoelastins. Together these data identify significant evolutionary constraints dictated by fundamental requirements for formation and functionality of the extracellular elastin matrix. Mutations/polymorphisms in human tropoelastin affecting such well-conserved characteristics might be expected to have phenotypic consequences.
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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 | 0.000 | 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".