WordNet

having a frequency below or above the range of human audibility; "a silent dog whistle"
marked by absence of sound; "a silent house"; "soundless footsteps on the grass"; "the night was still" (同)soundless, still
implied by or inferred from actions or statements; "gave silent consent"; "a tacit agreement"; "the understood provisos of a custody agreement" (同)tacit, understood
not made to sound; "the silent `h at the beginning of `honor"; "in French certain letters are often unsounded" (同)unsounded
(genetics) any event that changes genetic structure; any alteration in the inherited nucleic acid sequence of the genotype of an organism (同)genetic mutation, chromosomal_mutation
a change or alteration in form or qualities

PrepTutorEJDIC

『音がしない』,静かな / 『沈黙の』,口に出さない;音をたてない・無口の・《補語にのみ用いて》(…について)意見を述べていない,触れていない《+『about』(『on』)+『名』》 / 活動していない・(映画が)無声の・(文字が)発音されない・無声映画
変化,俸転 / (生物の)突然変異;その変種

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/03/10 11:25:30」(JST)

wiki en

Silent mutations are DNA mutations that do not result in a change to the amino acid sequence of a protein, or that do result in amino acid change but do not result in radically different properties of the changed amino acids. 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 acids' behaviors. Mutations that cause the altered codon to produce an amino acid with similar functionality (i.e. a mutation producing leucine instead of isoleucine) are often also classified as silent; if the properties of the amino acid are conserved, this mutation does not usually significantly affect protein function.^[1] 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.

Recent results suggest that silent mutations can have an effect on subsequent protein structure and activity.^[2]^[3]

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) a thousand times less UCC tRNA than UCU tRNA, then the incorporation of serine happens a thousand 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.

Secondary Messenger RNA structure

Silent mutations change the secondary structure of RNA. Since RNA has a secondary structure that is not necessarily linear like that of DNA, the shape that goes along with the complementary bonding in the structure can have significant effects. For example, if the RNA molecule is not very stable, then it can be broken down quickly by enzymes in the cytoplasm. Alternatively, if the RNA molecule is too stable, and the complementary bonds are too strong for unpacking before translation, then the gene can also be under expressed.

Also, if the oncoming ribosome pauses because of a knot in the RNA, then the polypeptide can have time to fold into an unusual structure before the tRNA molecule has time to add another amino acid.

Examples

Steffen Mueller at the Stony Brook University designed a live virus vaccine in which the pathogen was engineered to have synonymous codons take the place of normally occurring ones in the genome. As a result, the vaccine was still able to infect and reproduce, albeit more slowly. Mice were vaccinated with this vaccine and they showed a resistance against the natural polio strain.

Mental disorders can be caused by silent mutations. One silent mutation causes the dopamine receptor D2 gene to be less stable and degrade faster, under expressing the gene.

Also, deviations from average pain sensitivity (APS) are caused by both an ATG to GTG mutation (nonsynonymous), and a CAT to CAC mutation (synonymous). Ironically, these two mutations are both shared by the Low pain sensitivity (LPS) and High pain sensitivity (HPS)gene. What distinguishes LPS from HPS is that LPS has an additional CTC to CTG silent mutation, while HPS does not and shares the CTC sequence at this location with APS.

LPS	APS	HPS
CAC	CAT	CAC
CTG	CTC	CTC
GTG	ATG	GTG

A silent mutation in the multidrug resistance 1 gene, which codes for a cellular membrane pump that expels drugs from the cell, can slow down translation in a specific location to allow the peptide chain to bend into an unusual conformation. Thus, the mutant pump is less functional.

References

^ Alberts (2008). Molecular Biology of the Cell. Garland. pp. 264.
^ Komar (2006) SNPs, Silent But Not Invisible
^ 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. PMC 1734788. PMID 11768390. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1734788/. 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 (5811): 525–528. doi:10.1126/science.1135308. PMID 17185560. Abstract Summary Full Text

Chamary, J. V., and Laurence D. Hurst. "The price of silent mutations." Scientific American June 2009: 46-53. Print.

External links

Overview article in Scientific American
An online tool for silent mutagenesis
Mueller lab - recoding viral genomes through silent mutagnesis

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 無症候性心筋虚血：予後および治療 silent myocardial ischemia prognosis and therapy
2. 遺伝性疾患の基本原則 basic principles of genetic disease
3. 原発性免疫不全症に対する遺伝子治療 gene therapy for primary immunodeficiency
4. 無症候性心筋虚血：疫学、病態生理および診断 silent myocardial ischemia epidemiology pathophysiology and diagnosis
5. 心房細動の概要 overview of atrial fibrillation

English Journal

A functionally critical single nucleotide polymorphism in the gene encoding the membrane-bound alcohol dehydrogenase found in ethanol oxidation-deficient Gluconobacter thailandicus.

Charoenyingcharoen P1, Matsutani M2, Yakushi T3, Theeragool G4, Yukphan P5, Matsushita K6.
Gene.Gene.2015 Aug 10;567(2):201-7. doi: 10.1016/j.gene.2015.04.080. Epub 2015 May 2.
The Gluconobacter thailandicus strains NBRC3254, NBRC3255, NBRC3256, NBRC3257, and NBRC3258 are naturally deficient in the ethanol-oxidizing respiratory chain because they do not produce the cytochrome subunit of the membrane-bound alcohol dehydrogenase (ADH). Draft genomes of G. thailandicus strain
PMID 25943635

Amino- and Carboxyl-Terminal CCR5 Mutations in Brazilian HIV-1-Infected Women and Homology Model of p.L55Q CCR5 Mutant.

Costa GC1,2, Nunes MR3, Jesus JG1, Novaes T1, Cardoso JF3, Sousa Júnior EC3, Santos ES1, Galvão-Castro B1, Zanette DL1, Gonçalves MS1,2, Alcantara LC1.
AIDS research and human retroviruses.AIDS Res Hum Retroviruses.2015 Jul;31(7):685-691. Epub 2015 Apr 29.
Genetic factors from an HIV-1 host can affect the rate of progression to AIDS and HIV infection. To investigate the frequency of mutations in the CCR5 gene, HIV-1 samples from infected women and uninfected individuals were selected for sequencing of the CCR5 gene regions encoding the N- and C-termin
PMID 25825809

Japanese Journal

分子病の質量分析：Δmによる分子診断

和田芳直
Journal of the Mass Spectrometry Society of Japan = 質量分析 61(4), 35-41, 2013
… A distinct merit of MS was its ability to detect "silent" mutations which are not amenable to conventional analytical methods including electrophoresis and chromatography. …
NAID 130003366692

Efficient Genetic Analysis of Microdissected Samples by Agarose-Bead Method: Alterations of β-Catenin Gene in Fundic Gland Polyp and Heterotopic Gastric Mucosa of Duodenum

Nakagawa Miku,Kitazawa Riko,Kuwahara Natsumi,Yoshida Keisuke,Haraguchi Ryuma,Kitazawa Sohei
ACTA HISTOCHEMICA ET CYTOCHEMICA 46(1), 19-24, 2013
… In the present study, to elucidate the contribution of β-catenin gene mutation to the fundic gland polyp and the heterotopic gastric mucosa in the duodenum, we successfully introduced an agarose-bead mediated technique as an effectual tool for retrospective morphology-oriented genetic analyses. … A fragment of the agarose-bead was used as a template for polymerase chain reaction to analyze β-catenin mutation. …
NAID 130003361065