Mughal Fizza, Caetano-Anollés Gustavo
Evolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of Illinois, Urbana, IL, 61801, USA.
C.R. Woese Institute for Genomic Biology, University of Illinois, Urbana, IL, 61801, USA.
Sci Rep. 2025 Jan 22;15(1):2878. doi: 10.1038/s41598-025-86045-4.
Intrinsically disordered regions are flexible regions that complement the typical structured regions of proteins. Little is known however about their evolution. Here we leverage a comparative and evolutionary genomics approach to analyze intrinsic disorder in the structural domains of thousands of proteomes. Our analysis revealed that viral and cellular proteomes employ similar strategies to increase disorder but achieve different goals. Viral proteomes evolve disorder for economy of genomic material and multifunctionality. On the other hand, cellular proteomes evolve disorder to advance functionality with increasing genomic complexity. Remarkably, phylogenomic analysis of intrinsic disorder showed that ancient domains were ordered and that disorder evolved as a benefit acquired later in evolution. Evolutionary chronologies of domains indexed with disorder levels and distributions across Archaea, Bacteria, Eukarya and viruses revealed six evolutionary phases, the oldest two harboring only ordered and moderate disorder domains. A biphasic spectrum of disorder versus proteome makeup captured the dichotomy in the evolutionary trajectories of viral and cellular ancestors, one following reductive evolution driven by viral spread of molecular wealth and the other following expansive evolutionary trends to advance functionality through massive domain-forming co-option of disordered loop regions.
内在无序区域是与蛋白质典型结构区域互补的灵活区域。然而，关于它们的进化却知之甚少。在这里，我们利用比较和进化基因组学方法来分析数千个蛋白质组结构域中的内在无序性。我们的分析表明，病毒和细胞蛋白质组采用相似的策略来增加无序性，但目标不同。病毒蛋白质组为了基因组材料的经济性和多功能性而进化出无序性。另一方面，细胞蛋白质组随着基因组复杂性的增加而进化出无序性以提升功能。值得注意的是，对内在无序性的系统发育基因组分析表明，古老的结构域是有序的，无序性是在进化后期获得的一种优势。根据古菌、细菌、真核生物和病毒中无序水平和分布对结构域进行索引的进化年代表揭示了六个进化阶段，最古老的两个阶段只包含有序和中度无序的结构域。无序性与蛋白质组组成的双相谱捕捉到了病毒和细胞祖先进化轨迹的二分法，一种是由分子财富的病毒传播驱动的还原进化，另一种是通过大量无序环区域的结构域形成共选择来推进功能的扩张进化趋势。
