Molecular and Cellular Imaging Center (MCIC), Ohio Agricultural and Research Development Center (OARDC), Ohio State University, Wooster, OH, United States of America.
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, United States of America.
PLoS Comput Biol. 2018 Apr 30;14(4):e1006098. doi: 10.1371/journal.pcbi.1006098. eCollection 2018 Apr.
Understanding complexity in physical, biological, social and information systems is predicated on describing interactions amongst different components. Advances in genomics are facilitating the high-throughput identification of molecular interactions, and graphs are emerging as indispensable tools in explaining how the connections in the network drive organismal phenotypic plasticity. Here, we describe the architectural organization and associated emergent topological properties of gene regulatory networks (GRNs) that describe protein-DNA interactions (PDIs) in several model eukaryotes. By analyzing GRN connectivity, our results show that the anticipated scale-free network architectures are characterized by organism-specific power law scaling exponents. These exponents are independent of the fraction of the GRN experimentally sampled, enabling prediction of properties of the complete GRN for an organism. We further demonstrate that the exponents describe inequalities in transcription factor (TF)-target gene recognition across GRNs. These observations have the important biological implication that they predict the existence of an intrinsic organism-specific trans and/or cis regulatory landscape that constrains GRN topologies. Consequently, architectural GRN organization drives not only phenotypic plasticity within a species, but is also likely implicated in species-specific phenotype.
理解物理、生物、社会和信息系统中的复杂性,需要描述不同组件之间的相互作用。基因组学的进步正在促进分子相互作用的高通量识别,图作为解释网络连接如何驱动生物体表型可塑性的不可或缺的工具正在出现。在这里,我们描述了描述几种模式真核生物中蛋白质-DNA 相互作用(PDI)的基因调控网络(GRN)的结构组织和相关涌现的拓扑性质。通过分析 GRN 的连接性,我们的结果表明,预期的无标度网络架构的特点是具有特定于生物体的幂律标度指数。这些指数独立于实验采样的 GRN 部分,能够预测生物体完整 GRN 的属性。我们进一步证明,这些指数描述了 GRN 中转录因子(TF)-靶基因识别的不平等。这些观察结果具有重要的生物学意义,它们预测了存在内在的、特定于生物体的转和/或顺式调节景观,限制了 GRN 的拓扑结构。因此,结构 GRN 组织不仅驱动了一个物种内的表型可塑性,而且可能与物种特异性表型有关。