Evolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of Illinois, Urbana, IL, 61801, USA.
Sci Rep. 2021 Jun 8;11(1):12075. doi: 10.1038/s41598-021-90498-8.
Domains are the structural, functional and evolutionary units of proteins. They combine to form multidomain proteins. The evolutionary history of this molecular combinatorics has been studied with phylogenomic methods. Here, we construct networks of domain organization and explore their evolution. A time series of networks revealed two ancient waves of structural novelty arising from ancient 'p-loop' and 'winged helix' domains and a massive 'big bang' of domain organization. The evolutionary recruitment of domains was highly modular, hierarchical and ongoing. Domain rearrangements elicited non-random and scale-free network structure. Comparative analyses of preferential attachment, randomness and modularity showed yin-and-yang complementary transition and biphasic patterns along the structural chronology. Remarkably, the evolving networks highlighted a central evolutionary role of cofactor-supporting structures of non-ribosomal peptide synthesis pathways, likely crucial to the early development of the genetic code. Some highly modular domains featured dual response regulation in two-component signal transduction systems with DNA-binding activity linked to transcriptional regulation of responses to environmental change. Interestingly, hub domains across the evolving networks shared the historical role of DNA binding and editing, an ancient protein function in molecular evolution. Our investigation unfolds historical source-sink patterns of evolutionary recruitment that further our understanding of protein architectures and functions.
结构域是蛋白质的结构、功能和进化单位。它们组合形成多结构域蛋白质。这种分子组合的进化历史已经通过系统发生基因组学方法进行了研究。在这里，我们构建了结构域组织网络，并探索了它们的进化。时间序列网络揭示了两次古老的结构新颖性浪潮，分别源自古老的“p 环”和“翼状螺旋”结构域，以及大量的“大爆炸”结构域组织。结构域的进化招募具有高度模块化、层次化和持续的特点。结构域重排引发了非随机和无标度的网络结构。偏好连接、随机性和模块性的比较分析表明，沿着结构年代学存在阴阳互补的转变和双相模式。值得注意的是，进化网络突出了非核糖体肽合成途径中辅助因子支持结构的核心进化作用，这可能对遗传密码的早期发展至关重要。一些高度模块化的结构域在具有 DNA 结合活性的双组分信号转导系统中具有双重响应调节功能，与对环境变化的转录调节相关。有趣的是，进化网络中的枢纽结构域共享 DNA 结合和编辑的历史作用，这是分子进化中的一种古老蛋白质功能。我们的研究揭示了进化招募的历史源汇模式，进一步加深了我们对蛋白质结构和功能的理解。
