Silent mutation
Encyclopedia
Silent mutations are DNA
mutation
s 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 bias
es, 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.
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
.
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.
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.
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s that do not result in a change to the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
sequence of a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
. They may occur in a non-coding region
Noncoding DNA
In genetics, noncoding DNA describes components of an organism's DNA sequences that do not encode for protein sequences. In many eukaryotes, a large percentage of an organism's total genome size is noncoding DNA, although the amount of noncoding DNA, and the proportion of coding versus noncoding...
(outside of a gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
or within an intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
), or they may occur within an exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
in a manner that does not alter the final amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
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
Neutral theory of molecular evolution
The neutral theory of molecular evolution states that the vast majority of evolutionary changes at the molecular level are caused by random drift of selectively neutral mutants . The theory was introduced by Motoo Kimura in the late 1960s and early 1970s...
. However, many organisms are known to exhibit codon usage bias
Codon usage bias
Codon usage bias refers to differences in the frequency of occurrence of synonymous codons in coding DNA. A codon is a series of three nucleotides that encodes a specific amino acid residue in a polypeptide chain or for the termination of translation .There are 64 different codons but only 20...
es, suggesting that there is selection
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....
for the use of particular codons due to translational stability. Silent mutations may also affect splicing
Splicing (genetics)
In molecular biology and genetics, splicing is a modification of an RNA after transcription, in which introns are removed and exons are joined. This is needed for the typical eukaryotic messenger RNA before it can be used to produce a correct protein through translation...
, or transcriptional control
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
.
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.
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 structureSecondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
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
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within 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
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
.
Examples
Steffen MuellerSteffen Mueller
Steffen Mueller is an American virologist and synthetic biologist. He is an Assistant Professor at Stony Brook University in New York.Mueller received his Ph.D...
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
Dopamine receptor D2
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...
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.
See also
- Degeneracy of the genetic code
- Genealogical DNA testGenealogical DNA testA genealogical DNA test examines the nucleotides at specific locations on a person's DNA for genetic genealogy purposes. The test results are not meant to have any informative medical value and do not determine specific genetic diseases or disorders ; they are intended only to give genealogical...
- Missense mutationMissense mutationIn genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional...
- Nonsense mutationNonsense mutationIn genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product. It differs from a missense mutation, which is a point mutation...
- Point mutationPoint mutationA point mutation, or single base substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic material, DNA or RNA. Often the term point mutation also includes insertions or deletions of a single base pair...