The sarcomere-based structure of muscles is conserved among vertebrates; however, vertebrate muscle physiology is extremely diverse. A molecular explanation for this diversity and its evolution has not been proposed. We use phylogenetic analyses and single-molecule force spectroscopy (smFS) to investigate the mechanochemical evolution of titin, a giant protein responsible for the elasticity of muscle filaments. We resurrect eight-domain fragments of titin corresponding to the common ancestors to mammals, sauropsids, and tetrapods, which lived 105–356 Myr ago, and compare them with titin fragments from some of their modern descendants. We demonstrate that the 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 seems to correlate with animal body size, allowing us to estimate the sizes of extinct species. We hypothesize that mechanical adjustments in titin contributed to physiological changes that allowed the muscular development and diversity of modern tetrapods.

中文翻译：

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从复活的蛋白质推断出巨大的肌肉蛋白质滴定蛋白的力学化学演化

在脊椎动物中，基于肌节的肌肉结构是保守的。但是，脊椎动物的肌肉生理学极为多样。尚未提出这种多样性及其演变的分子解释。我们使用系统发育分析和单分子力谱（smFS）来研究titin的机械化学演变，titin是负责肌肉细丝弹性的巨大蛋白质。我们复活了在哺乳动物，蜥脚类动物和四足动物（生活在105-356迈尔之前）中对应于titan的八域片段，并将它们与一些现代后代的titin片段进行比较。我们证明复活的泰坦分子富含二硫键并显示出较高的机械稳定性。这些机械化学元素已经随着时间而改变，产生了与动物体型相关的古力学趋势，从而使我们能够估计灭绝物种的大小。我们假设，替丁的机械调节有助于生理变化，从而允许现代四足动物的肌肉发育和多样性。