Data from: The causes of epistasis in genetic networks

Epistasis refers to the non-additive interactions between genes in determining phenotypes. Considerable efforts have shown that, even for a given organism, epistasis may vary both in intensity and sign. Recent comparative studies supported that the overall sign of epistasis switches from positive to negative as the complexity of an organism increases, and it has been hypothesized that this change shall be a consequence of the underlying gene network properties. Why should this be the case? What characteristics of genetic networks determine the sign of epistasis? Here we show, by evolving genetic networks that differ in their complexity and robustness against perturbations but that perform the same tasks, that robustness increased with complexity and that epistasis was positive for small non-robust networks but negative for large robust ones. Our results indicate that robustness and negative epistasis emerge as a consequence of the existence of redundant elements in regulatory structures of genetic networks and that the correlation between complexity and epistasis is a byproduct of such redundancy, allowing for the decoupling of epistasis from the underlying network complexity.上位性（Epistasis）指基因在决定表型（phenotypes）过程中所发生的非加性相互作用。大量研究证实，即便针对同一生物体，上位性的强度与符号均可发生变化。近期的比较研究证实，随着生物体复杂度的提升，上位性的整体符号会由正向转为负向，且有假说指出这一变化源于底层基因网络（genetic networks）的固有属性。为何会出现这一现象？基因网络的哪些特征决定了上位性的符号？本研究通过演化得到复杂度、抗扰动鲁棒性各异但执行相同任务的基因网络，证实鲁棒性随复杂度提升而增强，且小型非鲁棒网络的上位性为正向，大型鲁棒网络的上位性则为负向。研究结果表明，鲁棒性与负向上位性源于基因网络调控结构中冗余元件的存在，而复杂度与上位性的相关性正是此类冗余的附带产物，这使得上位性得以脱离底层网络的复杂度而独立存在。