involvement. It is advised to measure cardiac troponin I instead if a skeletal muscle disorder is suspected. Elevated levels after Covid-19 mRNA vaccinations A study carried out by the University of Basel and the University Hospital of Basel found that a Covid-19 mRNA vaccination significantly elevates the cardiac troponin T levels in the blood stream. 3 % of the study subjects have shown elevated amounts of the protein after their 3rd vaccination. The effect was most pronounced among young men. It is not yet clear what the mechanism is, and the observed troponin levels were still much lower than in clinically significant heart disease. Given that previous studies only registered 35 cases of heart muscle inflammation per million subjects, the involved researchers were surprised by the results. Evolution Three homologous genes have evolved in vertebrates encoding three muscle type- specific isoforms of TnT. Each of the TnT isoform genes is linked in chromosomal DNA to a troponin I (TnI) isoform gene encoding the inhibitory subunit of the troponin complex to form three gene pairs: The fast skeletal muscle TnI (fsTnI)-fsTnT, slow skeletal muscle TnI (ssTnI)-cTnT, and cTnI-ssTnT pairs. Sequence and epitope conservation studies suggested that genes encoding the muscle type-specific TnT and TnI isoforms have originated from a TnI-like ancestor gene and duplicated and diversified from a fsTnI-like-fsTnT-like gene pair. The apparently scrambled linkage between ssTnI-cTnT and cTnI-ssTnT genes actually reflects original functional linkages as that TNNT2 gene is expressed together with ssTnI gene in embryonic cardiac muscle. Protein sequence alignment demonstrated that TNNT2 gene is conserved in vertebrate species (Fig. 2) in the middle and C-terminal regions, while the three muscle type isoforms are significantly diverged. Alternative splicing Mammalian TNNT2 gene contains 14 constitutive exons and 3 alternatively spliced exons. Exons 4 and 5 encoding the N-terminal variable region and exon 13 between the middle and C-terminal regions are alternatively spliced. Exon 5 encodes a 9 or 10 amino acid segment that is highly acidic and negatively charged at physiological pH. Exon 5 is expressed in embryonic heart, down-regulated and ceases express during postnatal development. Embryonic cTnT with more negative charge at the N-terminal region exerts higher calcium sensitivity of actomyosin ATPase activity and myofilament force production, compared with the adult cardiac TnT, as well as a higher tolerance to acidosis. TNNT2 gene is transiently expressed in embryonic and neonatal skeletal muscles in both avian and mammalian organisms. When