Department of Medical Oncology and Experimental Therapeutics, City of Hope, National Medical Center, Duarte, CA 91010, USA.
Biomolecules. 2020 Oct 28;10(11):1490. doi: 10.3390/biom10111490.
The past quarter-century may justly be referred to as a period analogous to the "Cambrian explosion" in the history of proteins. This period is marked by the appearance of the intrinsically disordered proteins (IDPs) on the scene since their discovery in the mid-1990s. Here, I first reflect on how we accidentally stumbled on these fascinating molecules. Next, I describe our research on the IDPs over the past decade and identify six areas as important for future research in this field. In addition, I draw on discoveries others in the field have made to present a more comprehensive essay. More specifically, I discuss the role of IDPs in two fundamental aspects of life: in phenotypic switching, and in multicellularity that marks one of the major evolutionary transitions. I highlight how serendipity, imagination, and an interdisciplinary approach embodying empirical evidence and theoretical insights from the works of Poincaré, Waddington, and Lamarck, shaped our thinking, and how this led us to propose the MRK hypothesis, a conceptual framework addressing phenotypic switching, the emergence of new traits, and adaptive evolution via nongenetic and IDP conformation-based mechanisms. Finally, I present a perspective on the evolutionary link between phenotypic switching and the origin of multicellularity.
过去的四分之一个世纪可以恰当地被称为蛋白质历史上的“寒武纪大爆发”时期。自 20 世纪 90 年代中期发现以来,无序蛋白质(IDP)的出现标志着这一时期的到来。在这里,我首先反思了我们是如何偶然发现这些迷人分子的。接下来,我描述了我们在过去十年中对 IDP 的研究,并确定了该领域未来研究的六个重要领域。此外,我借鉴了该领域其他人的发现,提出了一篇更全面的文章。更具体地说,我讨论了 IDP 在生命的两个基本方面的作用:表型转换和标志着主要进化转变之一的多细胞性。我强调了偶然性、想象力以及体现了庞加莱、沃丁顿和拉马克著作中的实证证据和理论见解的跨学科方法如何塑造了我们的思维,以及这如何导致我们提出 MRK 假说,这一概念框架通过非遗传和 IDP 构象为基础的机制来解决表型转换、新特征的出现以及适应性进化的问题。最后,我提出了关于表型转换和多细胞性起源之间的进化联系的观点。