ArticleMolecular biology and evolution2022
Network Topology Can Explain Differences in Pleiotropy Between Cis- and Trans-regulatory Mutations.
Article in Molecular biology and evolution, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 7 citations in OpenAlex.
- Epistatic impacts of cis- and trans-regulatory mutations on the distribution of mutational effects for gene expression in Saccharomyces cerevisiae.Molecular biology and evolution · 2026Article
- Molecular evolution in light of regulatory-coding epistasis.EMBO reports · 2026Review
- A naturally synonymous mutation modulates an ERK-centered regulatory network to mediate thermotolerance divergence in Crassostrea oysters.Communications biology · 2026Article
- Read mismapping from segmental duplications drives spuriousbioRxiv : the preprint server for biology · 2025Article
- Pleiotropy, epistasis and the genetic architecture of quantitative traits.Nature reviews. Genetics · 2024Review
- Environmentally robustProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Contributions of mutation and selection to regulatory variation: lessons from thePhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.