Cardiac contraction velocity has evolved to match heart rate with body size through variation in β-cardiac myosin sequence

Abstract

AbstractHeart rate and the maximum velocity of contraction of striated muscle are inversely related to species size. As mammals evolve to different sizes, adaptations are required such as slower contracting heart and skeletal muscles. Analysis of the motor domain of β-myosin from 67 mammals from two clades identifies 14 sites, out of 800, strongly associated with body mass (p<0.01) but not with the clade (p>0.05). Nine of these sites were mutated in the human β-myosin to make it resemble the rat sequence. Biochemical analysis revealed that the rat-human β-myosin chimera functioned like the native rat myosin with a two fold increase in both motility and in the rate of ADP release from the actin.myosin cross-bridge (the step that limits contraction velocity). Both clades use the same small set of amino acids to adjust contraction velocity, suggesting a limited number of ways in which velocity can be manipulated.