A major presumption of the neutral theory of evolution proposed by Kimura in the late 1960s is that synonymous mutations (mutations that do not alter the primary sequence of a protein due to the redundancy of the genetic code) are supposed to be selectively neutral or nearly neutral (Kimura 1968). However, Shen et al. (2022) have recently demonstrated that 75.9% of synonymous mutations in genes involved in important cellular functions in the haploid yeast Saccharomyces cerevisiae show reduced fitness in different environments examined. Based on their analyses of fitness effects in different growth conditions, the authors argue that non-synonymous mutants show a more significant fitness variation across growth environments compared with synonymous mutants, although the two mutant classes have similar patterns of fitness susceptibility in the same environment. They propose that a larger proportion of synonymous mutants reach fixation compared with their non-synonymous counterparts because more of them survive environmental challenges. In this Clipboard article, I examine the evidence provided by the authors to evaluate whether their evidence is sufficient to substantiate this claim and explore possible consequences of these observations.
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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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