Dynamic epistasis under varying environmental perturbations.
Dynamic epistasis under varying environmental perturbations.
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DOI：
10.1371/journal.pone.0114911
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Gu Z
中科院分区：
文献类型：
--
作者：
Barker B;Xu L;Gu Z
上位性描述了不同基因座的突变对某些表型没有独立影响的现象。了解全球上位景观对于许多遗传和进化理论至关重要。目前对多种条件下上位动力学的了解受到实验筛选基因间上位关系的技术困难的限制。我们通过应用通量平衡分析来模拟各种环境扰动下的上位景观来探讨这个问题。具体来说，我们研究了基因与基因上位相互作用，其中假设突变发生在不同的基因中。我们预测，从葡萄糖丰富的条件到营养限制的条件，上位性往往会变得更加积极，这表明选择在消除后者的有害突变方面可能不太有效。我们还在所有测试条件下观察到了稳定的上位相互作用核心，以及每种条件下独特的许多上位相互作用。有趣的是，稳定的上位相互作用网络中的基因与大多数其他基因直接相关，而具有条件特异性上位的基因形成无标度网络。此外，具有稳定上位性的基因往往具有相似的进化速率，而这种共同进化关系对于具有条件特异性上位性的基因并不成立。我们的研究结果提供了关于环境扰动下上位动力学的新的全基因组图景。
Epistasis describes the phenomenon that mutations at different loci do not have independent effects with regard to certain phenotypes. Understanding the global epistatic landscape is vital for many genetic and evolutionary theories. Current knowledge for epistatic dynamics under multiple conditions is limited by the technological difficulties in experimentally screening epistatic relations among genes. We explored this issue by applying flux balance analysis to simulate epistatic landscapes under various environmental perturbations. Specifically, we looked at gene-gene epistatic interactions, where the mutations were assumed to occur in different genes. We predicted that epistasis tends to become more positive from glucose-abundant to nutrient-limiting conditions, indicating that selection might be less effective in removing deleterious mutations in the latter. We also observed a stable core of epistatic interactions in all tested conditions, as well as many epistatic interactions unique to each condition. Interestingly, genes in the stable epistatic interaction network are directly linked to most other genes whereas genes with condition-specific epistasis form a scale-free network. Furthermore, genes with stable epistasis tend to have similar evolutionary rates, whereas this co-evolving relationship does not hold for genes with condition-specific epistasis. Our findings provide a novel genome-wide picture about epistatic dynamics under environmental perturbations.
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