Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
Translational Tissue Engineering Center, Department of Biomedical Engineering and Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Protein Sci. 2022 Apr;31(4):822-834. doi: 10.1002/pro.4270. Epub 2022 Feb 12.
Intrinsically disordered proteins (IDPs) effect biological function despite their sequence-encoded lack of preference for stable three-dimensional structure. Among their many functions, IDPs form membraneless cellular compartments through liquid-liquid phase separation (LLPS), also termed biomolecular condensation. The extent to which LLPS has been evolutionarily selected remains largely unknown, as the complexities of IDP evolution hamper progress. Unlike structured proteins, rapid sequence divergence typical of IDPs confounds inference of their biophysical or biological functions from comparative sequence analyses. Here, we leverage mitosis as a universal eukaryotic feature to interrogate condensate evolutionary history. We observe that evolution has conserved the ability for six homologs of the mitotic IDP BuGZ to undergo LLPS and to serve the same mitotic function, despite low sequence conservation. We also observe that cellular context may tune LLPS. The phylogenetic correlation of LLPS and mitotic function in one protein raises the possibility of an ancient evolutionary interplay between LLPS and biological function, dating back at least 1.6 billion years to the last common ancestor of plants and animals.
无规则蛋白质（IDPs）尽管其序列编码缺乏对稳定三维结构的偏好，但仍能发挥生物功能。在它们的许多功能中，IDPs 通过液-液相分离（LLPS）形成无膜细胞区室，也称为生物分子凝聚。LLPS 在多大程度上受到进化选择仍然很大程度上未知，因为 IDP 进化的复杂性阻碍了进展。与结构蛋白不同，IDP 的快速序列变异typical 使其从比较序列分析推断其生物物理或生物学功能变得复杂。在这里，我们利用有丝分裂作为普遍的真核特征来探究凝聚物的进化历史。我们观察到，尽管序列保守性低，但有丝分裂 IDP BuGZ 的六个同源物仍然具有进行 LLPS 的能力，并具有相同的有丝分裂功能。我们还观察到细胞环境可能会调节 LLPS。一种蛋白质中 LLPS 与有丝分裂功能的系统发育相关性提出了 LLPS 与生物功能之间可能存在古老的进化相互作用的可能性，至少可以追溯到 16 亿年前，即植物和动物的最后共同祖先。
