A silent mutation is a change in a gene’s nucleotide sequence that does not alter the amino acid sequence of the encoded protein because of the redundancy in the genetic code.
Explanation
Because multiple codons can specify the same amino acid, substitution of a single base in a codon may leave the translated protein unchanged. Such synonymous mutations often occur at the third nucleotide position of a codon, where “wobble” pairing allows several codons to be read by the same tRNA. Silent mutations can arise spontaneously during DNA replication or as a result of mutagens. They are sometimes called neutral mutations because they do not change the primary structure of the protein, but their effects are not always biologically trivial. Altering a codon can influence mRNA splicing, stability or secondary structure, and it can affect translation efficiency if the new codon uses a tRNA species that is less abundant or alters ribosome pausing. Synonymous variants can also disrupt regulatory motifs in mRNA or DNA. Distinguishing a truly silent mutation from those with subtle phenotypic effects requires careful molecular analysis.
Examples and research
In cystic fibrosis, a synonymous c.1525A>G mutation in the CFTR gene creates a cryptic splice site that reduces functional protein production. Synonymous mutations introduced into viral genomes during vaccine development can attenuate viruses by altering codon usage and lowering translation rates. Molecular biologists sometimes engineer silent mutations to create or remove restriction enzyme sites without changing protein sequence. Comparative genomics has revealed that silent mutations can accumulate at high rates in regions of genomes under weak selective pressure, whereas genes with strong codon usage bias may select for specific synonymous codons. Studies of human pharmacogenomics have found that certain silent variants in drug-metabolising enzymes can alter mRNA folding and affect enzyme levels.
Silent mutations illustrate that changes in DNA sequence can have consequences beyond the amino acid code, influencing gene expression and evolution.
Related Terms:Synonymous codon, Point mutation, Missense mutation, Codon usage, Genetic code.