ArticleGenome research2016
The nonessentiality of essential genes in yeast provides therapeutic insights into a human disease.
Article in Genome research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- ADSL deficiency is a secondary mitochondrial disease affecting organelle homeostasis and ERK2/AKT signaling in a linear genotype-phenotype relation.Cell reports · 2025Article
- Insights from human NF-κB knockouts.EMBO reports · 2025Review
- Recent advances in the characterization of essential genes and development of a database of essential genes.iMeta · 2024Review
- Adenylosuccinate lyase deficiency affects neurobehavior via perturbations to tyramine signaling in Caenorhabditis elegans.PLoS genetics · 2023Article
- Multiple intermolecular interactions facilitate rapid evolution of essential genes.Nature ecology & evolution · 2023Article
- Suppressor mutations that make the essential transcription factor Spn1/Iws1 dispensable in Saccharomyces cerevisiae.Genetics · 2022Article
- Systematic Identification of Essential Genes Required for Yeast Cell Wall Integrity: Involvement of the RSC Remodelling Complex.Journal of fungi (Basel, Switzerland) · 2022Article
- Rapid Intraspecies Evolution of Fitness Effects of Yeast Genes.Genome biology and evolution · 2022Article
- Transposon insertional mutagenesis of diverse yeast strains suggests coordinated gene essentiality polymorphisms.Nature communications · 2022Article
- Predicting miRNA-disease associations via layer attention graph convolutional network model.BMC medical informatics and decision making · 2022Article
- Article
- Mapping single-cell-resolution cell phylogeny reveals cell population dynamics during organ development.Nature methods · 2021Article
- Article
- Ancestry analysis indicates two different sets of essential genes in eukaryotic model species.Functional & integrative genomics · 2021Article
- Moderate levels of 5-fluorocytosine cause the emergence of high frequency resistance in cryptococci.Nature communications · 2021Article
- Essential genes from genome-wide screenings as a resource for neuropsychiatric disorders gene discovery.Translational psychiatry · 2021Article
- Genotype to Phenotype: CRISPR Gene Editing Reveals Genetic Compensation as a Mechanism for Phenotypic Disjunction of Morphants and Mutants.International journal of molecular sciences · 2021Review
- Combined embedding model for MiRNA-disease association prediction.BMC bioinformatics · 2021Article
- Article
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Essential genes refer to those whose null mutation leads to lethality or sterility. Theoretical reasoning and empirical data both suggest that the fatal effect of inactivating an essential gene can be attributed to either the loss of indispensable core cellular function (Type I), or the gain of fatal side effects after losing dispensable periphery function (Type II). In principle, inactivation of Type I essential genes can be rescued only by re-gain of the core functions, whereas inactivation of Type II essential genes could be rescued by a further loss of function of another gene to eliminate the otherwise fatal side effects. Because such loss-of-function rescuing mutations may occur spontaneously, Type II essential genes may become nonessential in a few individuals of a large population. Motivated by this reasoning, we here carried out a systematic screening for Type II essentiality in the yeast Saccharomyces cerevisiae Large-scale whole-genome sequencing of essentiality-reversing mutants reveals 14 cases whereby the inactivation of an essential gene is rescued by loss-of-function mutations on another gene. In particular, the essential gene encoding the enzyme adenylosuccinate lyase (ADSL) is shown to be Type II, suggesting a loss-of-function therapeutic strategy for the human disorder ADSL deficiency. A proof-of-principle test of this strategy in the nematode Caenorhabditis elegans shows promising results.
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