Identification of sequence changes in myosin II that adjust muscle contraction velocity

The speed of muscle contraction is related to body size; muscles in larger species contract at slower rates. Since a property the myosin isoform expressed muscle, we investigated how sequence changes range II isoforms enable this rate contraction. We considered 798 sequences from 13 mammalian identify any adaptation increasing mass. identified correlation between mass and divergence for motor domain 4 major adult (?/Type I, IIa, IIb, IIx), suggesting that these have adapted In contrast, non-muscle developmental show no with Analysis ?-myosin (predominant Type I/slow cardiac muscle) 67 mammals 2 distinct clades identifies 16 sites, out 800, associated (p adj < 0.05) but not clade > 0.05). Both change same small set amino acids, order large mammals, limited number ways which velocity can be successfully manipulated. To test relationship, 9 sites differ human rat were mutated match sequence. Biochemical analysis revealed rat–human chimera functioned like native 2-fold increase both motility ADP release actin–myosin crossbridge (the step limits velocity). Thus, indicate as increased reduced heart rate.