Silent mutation

Silent mutations are DNA mutations that do not result in a change to the amino acid sequence of a protein. They may occur in a non-coding region (outside of a gene or within an intron), or they may occur within an exon in a manner that does not alter the final amino acid sequence. The phrase silent mutation is often used interchangeably with the phrase synonymous mutation; however, synonymous mutations are a subcategory of the former, occurring only within exons.

Because silent mutations do not alter protein function they are often treated as though they are evolutionarily neutral. However, many organisms are known to exhibit codon usage biases, suggesting that there is selection for the use of particular codons due to translational stability. Silent mutations may also affect splicing, or transcriptional control.

In molecular cloning experiments, it can be useful to introduce silent mutations into a gene of interest in order to create or remove recognition sites for restriction enzymes. An online tool that can analyse a sequence of interest for possible mutations to create restriction sites is given in the External Links section.

Recent results suggest that silent mutations can have an effect on subsequent protein structure and activity^[1],^[2].

Transfer RNA

Transfer RNA(tRNA) availability is one of the reasons that a silent mutation might not be silent at all. For every codon there's a different tRNA molecule. So there's a tRNA specifically for the codon UCU and another specifically for the codon UCC (and so on for all the codons). Both of those tRNA molecules carry the amino-acid serine to the ribosome that is translating a mRNA molecule. However, if there's (for example) 1000 times less UCC tRNA then UCU tRNA, the incorporation of serine happens a 1000 times slower when a mutation causes the codon to change from UCU to UCC. If it takes longer for the amino-acids to reach the ribosome, translation takes longer. This results in a lower expression of a certain gene with that 'silent' mutation. Also, if the ribosome has to wait too long, it might terminate translation prematurely.

See also

• Degeneracy of the genetic code
• Genealogical DNA test

References

1. ^ Komar (2006) SNPs, Silent But Not Invisible
2. ^ Beckman (2006)The Sound of a Silent Mutation

• Chao HK, Hsiao KJ, Su TS (2001). "A silent mutation induces exon skipping in the phenylalanine hydroxylase gene in phenylketonuria". Hum Genet 108 (1): 14–9. doi:10.1007/s004390000435. PMID 11214902. 
• Montera M, Piaggio F, Marchese C, Gismondi V, Stella A, Resta N, Varesco L, Guanti G, Mareni C (2001). "A silent mutation in exon 14 of the APC gene is associated with exon skipping in a FAP family". J Med Genet 38 (12): 863–7. doi:10.1136/jmg.38.12.863. PMID 11768390.  Full text
• Chava Kimchi-Sarfaty, Jung Mi Oh, In-Wha Kim, Zuben E. Sauna, Anna Maria Calcagno, Suresh V. Ambudkar, Michael M. Gottesman (2007). "A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity". Science 315: 525–528. doi:10.1126/science.1135308. PMID 17185560.  Abstract Summary Full Text

External links

• Overview article in Scientific American
• An online tool for silent mutagenesis