ArticleMolecular systems biology2015
Negative feedback buffers effects of regulatory variants.
Article in Molecular systems biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Stabilizing and directional selection shape the genetic variation of gene expression in the transcriptome of Chlamydomonas.Molecular biology and evolution · 2026Article
- Opposing behavioral roles for a single gene in a species with a supergene polymorphism.bioRxiv : the preprint server for biology · 2026Article
- Translational buffering tunes gene expression in mice and humans.Genome biology · 2026Article
- Probing the limits of cis-acting gene regulation using a model of allelic imbalance quantitative trait loci.PLoS genetics · 2025Article
- Aberrant gene expression prediction across human tissues.Nature communications · 2025Article
- Evolutionary trade-off and mutational bias could favor transcriptional over translational divergence within paralog pairs.PLoS genetics · 2023Article
- Article
- Antagonistic regulatory effects of a single cis-acting expression quantitative trait locus between transcription and translation of the MRPL43 gene.BMC genomic data · 2022Article
- Parallel and population-specific gene regulatory evolution in cold-adapted fly populations.Genetics · 2021Article
- A thermostability perspective on enhancing physicochemical and cytological characteristics of octacalcium phosphate by doping iron and strontium.Bioactive materials · 2021Article
- Article
- mRNAs, proteins and the emerging principles of gene expression control.Nature reviews. Genetics · 2020Review
- Isoform-resolved correlation analysis between mRNA abundance regulation and protein level degradation.Molecular systems biology · 2020Article
- Hybrid Incompatibilities and Transgressive Gene Expression Between Two Closely Related Subspecies ofFrontiers in genetics · 2020Article
- Unraveling cis and trans regulatory evolution during cotton domestication.Nature communications · 2019Article
- Yeast genetic interaction screens in the age of CRISPR/Cas.Current genetics · 2019Review
- Genomic evidence of Y chromosome microchimerism in the endometrium during endometriosis and in cases of infertility.Reproductive biology and endocrinology : RB&E · 2019Article
- CRISPR/Cas9-induced monoallelic mutations in the cytosolic AGPase large subunit gene APL2 induce the ectopic expression of APL2 and the corresponding small subunit gene APS2b in rice leaves.Transgenic research · 2018Article
- Genetics ofeLife · 2018Article
- The Evolution of Gene Expression in cis and trans.Trends in genetics : TIG · 2018Review
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanisms conferring robustness against regulatory variants have been controversial. Previous studies suggested widespread buffering of RNA misexpression on protein levels during translation. We do not find evidence that translational buffering is common. Instead, we find extensive buffering at the level of RNA expression, exerted through negative feedback regulation acting in trans, which reduces the effect of regulatory variants on gene expression. Our approach is based on a novel experimental design in which allelic differential expression in a yeast hybrid strain is compared to allelic differential expression in a pool of its spores. Allelic differential expression in the hybrid is due to cis-regulatory differences only. Instead, in the pool of spores allelic differential expression is not only due to cis-regulatory differences but also due to local trans effects that include negative feedback. We found that buffering through such local trans regulation is widespread, typically compensating for about 15% of cis-regulatory effects on individual genes. Negative feedback is stronger not only for essential genes, indicating its functional relevance, but also for genes with low to middle levels of expression, for which tight regulation matters most. We suggest that negative feedback is one mechanism of Waddington's canalization, facilitating the accumulation of genetic variants that might give selective advantage in different environments.
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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.