Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan, USA.
Mol Biol Evol. 2022 Dec 5;39(12). doi: 10.1093/molbev/msac266.
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.
突变的多效性程度（即它改变的特征数量）预计会影响突变对适应性的不利概率。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同一基因反式表达的突变具有更低的多效性，这表明顺式调控突变应该更少有害，并在进化时间中更有可能固定。在这里，我们使用酿酒酵母基因缺失菌株的表达和适应性数据来检验这些假设。通过将每个基因的缺失视为影响自身表达的顺式调控突变，而将其他基因的缺失影响该焦点基因的表达视为反式调控突变，我们发现顺式作用的突变确实比影响同一基因表达的反式作用突变具有更低的多效性。在数据集的绝大多数基因中都观察到了这种模式，这可以通过控制基因表达的调控网络的拓扑结构来解释。比较影响同一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的缺失往往更具危害性。这些发现为多效性在顺式调控等位基因的优先固定中发挥作用提供了强有力的支持。
