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.

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.