ArticleMolecular biology and evolution2021
Suboptimal Global Transcriptional Response Increases the Harmful Effects of Loss-of-Function Mutations.
Article in Molecular biology and evolution, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Signatures of nonsense-mediated mRNA decay but no evidence for transcriptional adaptation associated with protein-truncating variants in wild yeast diploids.Molecular biology and evolution · 2026Article
- A nanobody-based degron system for targeted protein knockdown in Dictyostelium discoideum.BMC molecular and cell biology · 2026Article
- MKRN1 as a prioritized drug target for postpartum depression: evidence from druggable proteome profiling and multi-layer validation.Translational psychiatry · 2026Article
- Transcriptomic and proteomic effects of gene deletion are not evolutionarily conserved.Genome research · 2025Article
- Article
- Prevalence of and gene regulatory constraints on transcriptional adaptation in single cells.Genome biology · 2024Article
- Active compensation for changes in TDH3 expression mediated by direct regulators of TDH3 in Saccharomyces cerevisiae.PLoS genetics · 2023Article
- Prevalence of and gene regulatory constraints on transcriptional adaptation in single cells.bioRxiv : the preprint server for biology · 2023Article
- The role of the Aspergillus nidulans high mobility group B protein HmbA, the orthologue of Saccharomyces cerevisiae Nhp6p.Scientific reports · 2022Article
- Convergent phenotypic evolution towards fosfomycin collateral sensitivity of Pseudomonas aeruginosa antibiotic-resistant mutants.Microbial biotechnology · 2022Article
- Dissecting the Fitness Costs of Complex Mutations.Molecular biology and evolution · 2021Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
The fitness impact of loss-of-function mutations is generally assumed to reflect the loss of specific molecular functions associated with the perturbed gene. Here, we propose that rewiring of the transcriptome upon deleterious gene inactivation is frequently nonspecific and mimics stereotypic responses to external environmental change. Consequently, transcriptional response to gene deletion could be suboptimal and incur an extra fitness cost. Analysis of the transcriptomes of ∼1,500 single-gene deletion Saccharomyces cerevisiae strains supported this scenario. First, most transcriptomic changes are not specific to the deleted gene but are rather triggered by perturbations in functionally diverse genes. Second, gene deletions that alter the expression of dosage-sensitive genes are especially harmful. Third, by elevating the expression level of downregulated genes, we could experimentally mitigate the fitness defect of gene deletions. Our work shows that rewiring of genomic expression upon gene inactivation shapes the harmful effects of mutations.
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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.