Institute of Science and Technology Austria, Klosterneuburg, Austria.
Institute of Integrative Biology, University of Liverpool, Merseyside, United Kingdom.
Elife. 2017 Nov 13;6:e28921. doi: 10.7554/eLife.28921.
Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site. In large part, this epistasis can be qualitatively attributed to the structure of the transcriptional regulatory system and could therefore be a common feature in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the constraints of individual components, thereby increasing phenotypic variation that selection could act on and facilitating adaptive evolution.
大多数表型是由特定相互作用的分子组成的分子系统决定的。然而，与单个组件不同，对于分子系统整体的突变效应分布知之甚少。我们通过独立地、然后同时地突变一个转录因子及其所抑制的相关启动子，来询问转录调控系统的突变效应分布与各组件分布有何不同。我们发现，与单个组件分布相比，系统分布表现出更大的表型变异——这种效应源于转录因子与其 DNA 结合位点之间的分子间上位性。在很大程度上，这种上位性可以从转录调控系统的结构上定性地归因，因此可能是原核生物的一个共同特征。违反直觉的是，分子间上位性可以减轻单个组件的约束，从而增加选择可以作用的表型变异，并促进适应性进化。
