ArticleGenetics2022
Multiple epistatic DNA variants in a single gene affect gene expression in trans.
Article in Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed, 19 citations in OpenAlex.
- High-resolution genotype-free mapping of genetic variation with CRI-SPA-Map.Genome research · 2026Article
- Article
- A genome-to-proteome map reveals how natural variants drive proteome diversity and shape fitness.Science (New York, N.Y.) · 2025Article
- High-resolution, genotype-free mapping of genetic variation with CRI-SPA-Map.bioRxiv : the preprint server for biology · 2025Article
- Trans-eQTL hotspots shape complex traits by modulating cellular states.Cell genomics · 2025Article
- A genome-to-proteome atlas charts natural variants controlling proteome diversity and forecasts their fitness effects.bioRxiv : the preprint server for biology · 2024Article
- Substrate-specific effects of natural genetic variation on proteasome activity.PLoS genetics · 2023Article
- Mechanisms of regulatory evolution in yeast.Current opinion in genetics & development · 2022Review
- Variation in ubiquitin system genes creates substrate-specific effects on proteasomal protein degradation.eLife · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
DNA variants that alter gene expression in trans are important sources of phenotypic variation. Nevertheless, the identity of trans-acting variants remains poorly understood. Single causal variants in several genes have been reported to affect the expression of numerous distant genes in trans. Whether these simple molecular architectures are representative of trans-acting variation is unknown. Here, we studied the large RAS signaling regulator gene IRA2, which contains variants with extensive trans-acting effects on gene expression in the yeast Saccharomyces cerevisiae. We used systematic CRISPR-based genome engineering and a sensitive phenotyping strategy to dissect causal variants to the nucleotide level. In contrast to the simple molecular architectures known so far, IRA2 contained at least seven causal nonsynonymous variants. The effects of these variants were modulated by nonadditive, epistatic interactions. Two variants at the 5'-end affected gene expression and growth only when combined with a third variant that also had no effect in isolation. Our findings indicate that the molecular basis of trans-acting genetic variation may be considerably more complex than previously appreciated.
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Registered trials
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.