Complex Systems Laboratory, ICREA-Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Evolution. 2012 Feb;66(2):586-96. doi: 10.1111/j.1558-5646.2011.01451.x. Epub 2011 Sep 20.
Epistasis refers to the nonadditive 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 nonrobust 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.
上位性是指在决定表型时基因之间的非加性相互作用。大量研究表明，即使对于给定的生物体，上位性的强度和符号也可能发生变化。最近的比较研究支持这样的观点，即随着生物体复杂性的增加，上位性的整体符号从正变为负，并且有人假设这种变化将是潜在基因网络特性的结果。为什么会这样呢？遗传网络的哪些特征决定了上位性的符号？在这里，我们通过进化具有不同复杂性和对扰动抵抗力的遗传网络来表明，随着复杂性的增加，稳健性增加，并且小的非稳健网络的上位性为正，但大的稳健网络的上位性为负。我们的结果表明，稳健性和负上位性是遗传网络调控结构中冗余元件存在的结果，而复杂性和上位性之间的相关性是这种冗余的副产品，允许上位性与基础网络复杂性解耦。
