An alternative route to robustness: The relationship between assortativity, in-components, and characteristic path length in gene regulatory networks

Gene regulatory networks (GRNs) comprise the interacting genes and gene products that drive genetic regulation within the cell. Because of the vital role they play in producing cell function, GRNs are robust to a variety of perturbations, including genetic mutation. There are multiple underlying causes for this robustness, including topological properties of GRNs, such as their degree distribution. Another topological property, assortativity, has recently been attributed to the robustness of GRNs. Assortative GRNs were found to have smaller in-components (ICs) than their disassortative counterparts, and this led to increased robustness to multiple types of genetic mutation. However, some assortative GRNs lacked the distinctive small ICs, yet were still robust. This suggests that assortativity affects robustness via multiple mechanisms, and unraveling these is a necessary step for understanding which specific features of GRNs give rise to their robustness. Here, we uncover a separate route by which assortativity affects robustness, whereby assortativity influences the characteristic path length of the GRN, which in turn alters robustness.