Mechanochemical evolution of the giant muscle protein tititn as inferred from resurrecter proteins

Abstract

The sarcomere-based structure of muscles is conserved among vertebrates; however, vertebrate muscle physiology is extremely diverse. A molecular explanation for this muscle diversity and its evolution has not been proposed. In this Thesis, We use phylogenetic analysis and single-molecule force spectroscopy (smFS) to investigate the mechanochemical evolution of titin, a giant protein responsible for the elasticity of muscle filaments. We bring back to life eight-domain fragments of titin corresponding to ancestors to mammals, sauropsids, and tetrapods, that lived 105-356 Myr, and compare them with some of their modern descendants. We demonstrate that resurrected titin molecules are rich in disulfide bonds and display high mechanical stability. These mechanochemical elements have changed over time creating a paleomechanical trend that correlates with animal body size, allowing us to estimate the size of extinct species. We hypothesize that mechanical adjustments in titin contributed to physiological changes that allowed the muscular development and diversity of modern tetrapods.