Network Topology Can Explain Differences in Pleiotropy Between Cis- and Trans-regulatory Mutations.
Network Topology Can Explain Differences in Pleiotropy Between Cis- and Trans-regulatory Mutations.
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网络拓扑可以解释顺式和反式调节突变之间的多效性差异。
DOI：
10.1093/molbev/msac266
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发表时间：
2022-12-05
影响因子：
10.7
通讯作者：
Wittkopp, Patricia J.
中科院分区：
文献类型：
--
作者：
Zande, Petra Vande;Wittkopp, Patricia J.
突变的多效性程度（即，它改变的性状的数量）被预测为影响突变对适应性有害的概率。对于影响基因表达的突变，假设顺式作用的突变通常比影响相同基因的反式表达的突变具有较少的多效性，这表明顺式调节突变应该是有害的，并且更有可能随着进化时间的推移而固定。在这里，我们使用酿酒酵母基因缺失菌株的表达和适应度数据来测试这些假设。通过将每个基因的缺失视为影响其自身表达的顺式调节突变，并将影响该焦点基因表达的其他基因的缺失视为反式调节突变，我们发现顺式作用突变确实倾向于比影响相同基因表达的反式作用突变少多效性。在数据集中的绝大多数基因中观察到这种模式，并且可以通过控制基因表达的调控网络的拓扑结构来解释。比较影响相同基因表达的顺式和反式作用突变的适应性也证实了反式作用缺失倾向于更有害。这些研究结果提供了强有力的支持多效性发挥作用的顺式调节等位基因在进化过程中的优先固定。
A mutation's degree of pleiotropy (i.e., the number of traits it alters) is predicted to impact the probability of the mutation being detrimental to fitness. For mutations that impact gene expression, mutations acting in cis have been hypothesized to generally be less pleiotropic than mutations affecting the same gene's expression in trans, suggesting that cis-regulatory mutations should be less deleterious and more likely to fix over evolutionary time. Here, we use expression and fitness data from Saccharomyces cerevisiae gene deletion strains to test these hypotheses. By treating deletion of each gene as a cis-regulatory mutation affecting its own expression and deletions of other genes affecting expression of this focal gene as trans-regulatory mutations, we find that cis-acting mutations do indeed tend to be less pleiotropic than trans-acting mutations affecting expression of the same gene. This pattern was observed for the vast majority of genes in the data set and could be explained by the topology of the regulatory network controlling gene expression. Comparing the fitness of cis- and trans-acting mutations affecting expression of the same gene also confirmed that trans-acting deletions tend to be more deleterious. These findings provide strong support for pleiotropy playing a role in the preferential fixation of cis-regulatory alleles over evolutionary time.
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影响因子：
2.1
作者：
Cantwell, George T.;Kirkley, Alec;Newman, M. E. J.
通讯作者：
Newman, M. E. J.
影响因子：
7
作者：
Emerson, J. J.;Hsieh, Li-Ching;Li, Wen-Hsiung
通讯作者：
Li, Wen-Hsiung
DOI：
10.1073/pnas.71.7.2848
发表时间：
1974-01-01
影响因子：
11.1
作者：
KIMURA, M;OHTA, T
通讯作者：
OHTA, T
影响因子：
4.4
作者：
FELD, SL
通讯作者：
FELD, SL
影响因子：
10.7
作者：
Maclean, Calum J.;Metzger, Brian P. H.;Zhang, Jianzhi
通讯作者：
Zhang, Jianzhi