Duncan NRI Faculty and Staff Publications
Publication Date
12-1-2022
Journal
The American Journal of Human Genetics
DOI
10.1016/j.ajhg.2022.10.016
PMID
36459978
PMCID
PMC9808499
PubMedCentral® Posted Date
12-1-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Saccharomyces cerevisiae, Mutation, Amino Acid Sequence, Biological Evolution, Genome, Human
Abstract
Synonymous mutations change the DNA sequence of a gene without affecting the amino acid sequence of the encoded protein. Although some synonymous mutations can affect RNA splicing, translational efficiency, and mRNA stability, studies in human genetics, mutagenesis screens, and other experiments and evolutionary analyses have repeatedly shown that most synonymous variants are neutral or only weakly deleterious, with some notable exceptions. Based on a recent study in yeast, there have been claims that synonymous mutations could be as important as nonsynonymous mutations in causing disease, assuming the yeast findings hold up and translate to humans. Here, we argue that there is insufficient evidence to overturn the large, coherent body of knowledge establishing the predominant neutrality of synonymous variants in the human genome.
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