Emergence and propagation of epistasis in metabolic networks.
Emergence and propagation of epistasis in metabolic networks.
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DOI：
10.7554/elife.60200
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发表时间：
2021-02-02
期刊：
影响因子：
7.7
通讯作者：
Kryazhimskiy S
中科院分区：
文献类型：
--
作者：
Kryazhimskiy S
上位性基因经常被用来探索基因之间的功能关系，它在进化中扮演着重要的角色。然而，我们缺乏理论来理解分子水平上的功能关系如何转化为整个有机体表型水平的上位性，例如适合性。在这里，我推导了两条规则，说明在具有一级动力学的分级代谢网络中，影响较小的突变之间的上位性如何从较低的表型传播到较高的表型，以及这种上位性如何依赖于拓扑。最重要的是，较低水平的弱上位性在传播到较高水平时可能会被扭曲。计算分析表明，在更现实的模型中，上位性很可能遵循类似的模式，尽管更复杂。这些结果表明，两两基因间的上位性应该是常见的，它一般取决于遗传背景和环境。此外，为高水平表型测量的上位性系数可能不足以完全推断潜在的功能关系。
Epistasis is often used to probe functional relationships between genes, and it plays an important role in evolution. However, we lack theory to understand how functional relationships at the molecular level translate into epistasis at the level of whole-organism phenotypes, such as fitness. Here, I derive two rules for how epistasis between mutations with small effects propagates from lower- to higher-level phenotypes in a hierarchical metabolic network with first-order kinetics and how such epistasis depends on topology. Most importantly, weak epistasis at a lower level may be distorted as it propagates to higher levels. Computational analyses show that epistasis in more realistic models likely follows similar, albeit more complex, patterns. These results suggest that pairwise inter-gene epistasis should be common, and it should generically depend on the genetic background and environment. Furthermore, the epistasis coefficients measured for high-level phenotypes may not be sufficient to fully infer the underlying functional relationships.
影响因子：
4.3
作者：
Pumir A;Shraiman B
通讯作者：
Shraiman B
影响因子：
12.3
作者：
Velenich A;Gore J
通讯作者：
Gore J