Silent mutations are genetic mutations where a change in the nucleotide sequence of DNA does not lead to any observable effect on the organism.
These mutations do not alter the amino acid sequence of the protein, nor do they affect the protein’s structure or function.
They are also referred to as neutral mutations because they do not cause any changes in the final protein product formed.
The existence of silent mutations is made possible by the redundancy in the genetic code—multiple codons can code for the same amino acid, allowing some nucleotide changes to still result in the same amino acid being incorporated into the protein.
Silent mutations are also known as synonymous mutations, though not all synonymous mutations are entirely silent.
Some synonymous mutations can influence key biological processes such as transcription, splicing, mRNA transport, and translation, which can potentially lead to phenotypic changes in the organism.
Since silent mutations generally do not change the resulting protein product, they are considered evolutionarily neutral.
However, research has shown that organisms often exhibit codon usage bias—preferring certain codons over others for the same amino acid due to factors like translational efficiency and stability—indicating that silent mutations may not always be completely neutral.
In certain cases, silent mutations can have effects when they occur in a homozygous state; the mutation may be silent and harmless in the heterozygous form but cause noticeable effects when both alleles carry the mutation.
Causes of Silent Mutation
Silent mutations can arise due to a variety of causes, ranging from spontaneous errors during DNA processing to alterations induced by external physical agents.
Spontaneous mutations typically occur during essential DNA processes such as DNA replication. These changes may result from replication errors or from the action of enzymes like nucleases that digest DNA.
Some spontaneous silent mutations can also occur during the repair of damaged DNA sequences when the repair process introduces changes in nucleotides.
Induced silent mutations are caused by external physical agents or chemical molecules, such as radiation or mutagenic chemicals, which alter the nucleotide sequence.
These mutagens change one nucleotide into another in such a way that the resulting codon still encodes the same amino acid, thereby leaving the protein unaffected.
In silent mutations, the change in the codon sequence does not lead to a change in the amino acid because both the original and the mutated codon correspond to the same amino acid in the genetic code.
Some mutations may occur in regions of the gene or protein that do not impact the protein’s structure or function, and thus the mutation remains silent.
In certain cases, even when a different amino acid is produced, if the new amino acid is structurally and functionally similar to the original one, the mutation may not have any significant impact on the final protein product and can therefore be regarded as silent.
Mechanism of Silent Mutation
Silent mutations operate through the same fundamental mechanisms as other types of mutations, where a change in the nucleotide sequence occurs due to factors like tautomerism or ionization.
Although the exact mechanism behind spontaneous mutations is not fully understood, they are believed to result from either the deletion of a nucleotide base or alterations in the structure and bonding behavior of nucleotide bases.
One of the most common mechanisms responsible for silent mutations is tautomerism, in which a nucleotide changes its chemical form from the keto form to the enol form.
Under normal conditions, nucleotides predominantly exist in the keto form and are capable of forming stable hydrogen bonds with complementary bases.
When a nucleotide switches to the enol form, its ability to form hydrogen bonds is disrupted, preventing it from properly pairing with other nucleotides during DNA replication, which can result in a mutation.
Another contributing mechanism is ionization, which may occur in the presence of ionizing radiation such as X-rays or ultraviolet (UV) light, altering the structure of nucleotides.
During DNA replication, errors can also arise if digestive enzymes like nucleases degrade portions of the DNA sequence, potentially leading to changes in nucleotide sequences.
In silent mutations, the change in the nucleotide is usually subtle and does not cause a significant alteration in the amino acid sequence of the protein.
Either the same amino acid is encoded by the altered codon, or a different amino acid with similar chemical and functional properties is produced, resulting in no observable change in the protein’s structure or function.
Applications of Silent Mutation
Although silent mutations do not cause an observable effect on the resulting protein, organisms often exhibit codon usage biases, suggesting that silent mutations may play a role in evolutionary processes and natural selection.
Silent mutations are valuable tools for studying the impact of various mutagens (such as chemicals or radiation) on different DNA sequences, helping researchers understand mutation mechanisms and mutagenic specificity.
They are useful in investigating the relationship between codons and the amino acids they encode, aiding in the detailed study of genetic coding and the redundancy of the genetic code.
Silent mutations can be inherited across generations in a heterozygous form without producing any noticeable effect. However, when these mutations become homozygous, they may lead to significant changes in the amino acid sequence, potentially altering the protein’s structure and function.
Researchers also use silent mutations to explore the functional properties of genes and analyze how various cellular processes—like transcription, splicing, and translation—affect the DNA segment and gene expression.
Examples of Silent Mutation
A classic example of a silent mutation occurs when a thymine (T) nucleotide in the DNA sequence is replaced by cytosine (C) in the TTC codon, changing it to TTT.
The corresponding mRNA codons for TTC and TTT are AAG and AAA, respectively.
Both AAG and AAA mRNA codons code for the same amino acid, lysine, meaning the amino acid sequence of the resulting protein remains unchanged despite the mutation.
This illustrates how a point mutation can alter the codon without changing the amino acid, resulting in no effect on the final protein product.
This phenomenon is made possible by the degeneracy of the genetic code, where multiple codons can encode the same amino acid, allowing some mutations to be silent.
References
Lai, C.-C., et al. (2018). The clinical relevance of silent mutations in relation to ciprofloxacin resistance in methicillin-resistant Staphylococcus aureus (MRSA). Infection and Drug Resistance, 11, 681–687. https://doi.org/10.2147/IDR.S159455
Bali, V., & Bebok, Z. (2015). Understanding how silent codon alterations affect protein synthesis and function. The International Journal of Biochemistry & Cell Biology, 64, 58–74. https://doi.org/10.1016/j.biocel.2015.03.011
Patel, U. R., et al. (2019). Investigating the impact of a silent mutation in the ω-subunit of Escherichia coli RNA polymerase: Structural transition leads to transcription inhibition. ACS Omega, 4(18), 17714–17725. https://doi.org/10.1021/acsomega.9b02103
Kashiwagi, A., et al. (2014). Role of silent mutations in the thermal adaptation of RNA bacteriophage Qβ. Journal of Virology, 88(19), 11459–11468. https://doi.org/10.1128/JVI.01127-14
Petry, F., & Loos, M. (2005). Frequent silent mutations observed in all forms of hereditary complement C1q deficiency. Immunogenetics, 57(8), 566–571. https://doi.org/10.1007/s00251-005-0023-z
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