Although synonymous mutations are commonly assumed neutral or nearly so, recent years have seen reports of fitness effects of synonymous mutations detected under laboratory conditions. In a previous study, we used genome editing to construct thousands of yeast mutants each carrying a synonymous or nonsynonymous mutation in one of 21 genes, and discovered that most synonymous and most nonsynonymous mutations are deleterious. A concern was raised that this observation could be caused by the fitness effects of potential CRISPR/Cas9 off-target edits and/or secondary mutations, and an experiment that would be refractory to such effects was proposed. Using genome sequencing, we here show that no CRISPR/Cas9 off-target editing occurred, although some mutants did carry secondary mutations. Analysis of mutants with negligible effects from secondary mutations and new data collected from the proposed experiment confirms the original conclusion. These findings, along with other reports of fitness effects of synonymous mutations from both case and systematic studies, necessitate a paradigm shift from assuming (near) neutrality of synonymous mutations.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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| Evidence ID | Analyze ID | File | Description |
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