Journal
JOURNAL OF MOLECULAR EVOLUTION
Volume 90, Issue 1, Pages 30-43Publisher
SPRINGER
DOI: 10.1007/s00239-021-10039-9
Keywords
Troponin; Heart; Proteins; Selection value
Funding
- National Institutes of Health [HL127691, HL138007]
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The troponin-based calcium regulation of muscle contraction emerged approximately 700 million years ago and has largely conserved functions during evolution. However, cardiac troponin I (TnI) in vertebrates has evolved specific muscle type-specific isoforms, including phosphorylation sites for beta-adrenergic regulation. This rapid evolution suggests a high selection value for vertebrate hearts to adapt to increased metabolic demands on land.
Troponin-based Ca2+ regulation of striated muscle contraction emerged approximately 700 million years ago with largely conserved functions during evolution. Troponin I (TnI) is the inhibitory subunit of troponin and has evolved into three muscle type-specific isoforms in vertebrates. Cardiac TnI is specifically expressed in the adult heart and has a unique N-terminal extension implicating a specific value during natural selection. The N-terminal extension of cardiac TnI in higher vertebrates contains beta-adrenergic-regulated protein kinase A (PKA) phosphorylation sites as a mechanism to enhance cardiac muscle relaxation and facilitate ventricular filling. Phylogenic studies showed that the N-terminal extension of cardiac TnI first emerged in the genomes of early tetrapods as well as primordial lobe-finned fishes such as the coelacanth whereas it is absent in ray-finned fish. This apparently rapid evolution of beta-adrenergic regulation of cardiac function suggests a high selection value for the heart of vertebrate animals on land to work under higher metabolic demands. Sequencing and PKA phosphorylation data showed that lungfish cardiac TnI has evolved with an amphibian-like N-terminal extension with prototype PKA phosphorylation sites while its overall structure remained fish like. The data demonstrate that the submolecular structure of TnI may evolve ahead of the whole protein for cardiac muscle contractility to adapt to new environmental conditions. Understanding the evolution of the beta-adrenergic regulation of TnI and cardiac adaptation to the increased energetic demands of life on land adds knowledge for the treatment of human heart diseases and failure.
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