Silent mutation

Silent mutations are mutations in DNA that do not have an observable effect on the organism's phenotype. They are a specific type of neutral mutation. The phrase silent mutation is often used interchangeably with the phrase synonymous mutation; however, synonymous mutations are not always silent, nor vice versa. Synonymous mutations can affect transcription, splicing, mRNA transport, and translation, any of which could alter phenotype, rendering the synonymous mutation non-silent. The substrate specificity of the tRNA to the rare codon can affect the timing of translation, and in turn the co-translational folding of the protein. This is reflected in the codon usage bias that is observed in many species. Mutations that cause the altered codon to produce an amino acid with similar functionality (e.g. a mutation producing leucine instead of isoleucine) are often classified as silent; if the properties of the amino acid are conserved, this mutation does not usually significantly affect protein function. Silent mutations are mutations in DNA that do not have an observable effect on the organism's phenotype. They are a specific type of neutral mutation. The phrase silent mutation is often used interchangeably with the phrase synonymous mutation; however, synonymous mutations are not always silent, nor vice versa. Synonymous mutations can affect transcription, splicing, mRNA transport, and translation, any of which could alter phenotype, rendering the synonymous mutation non-silent. The substrate specificity of the tRNA to the rare codon can affect the timing of translation, and in turn the co-translational folding of the protein. This is reflected in the codon usage bias that is observed in many species. Mutations that cause the altered codon to produce an amino acid with similar functionality (e.g. a mutation producing leucine instead of isoleucine) are often classified as silent; if the properties of the amino acid are conserved, this mutation does not usually significantly affect protein function. The genetic code translates mRNA nucleotide sequences to amino acid sequences. Genetic information is coded using this process with groups of three codons along the mRNA which are commonly known as codons. The set of three nucleotides almost always produce the same polypeptide with are a few exceptions like UGA which typically serves as the stop codon but can also encode tryptophan in mammalian mitochondria. Most amino acids are specified by multiple codons demonstrating that the genetic code is degenerate–different codons result in the same amino acid. Codons that code for the same amino acid are termed synonyms. Silent mutations are base substitutions that result in no change of the amino acid or amino acid functionality when the altered messenger RNA (mRNA) is translated. For example, if the codon AAA is altered to become AAG, the same amino acid – lysine – will be incorporated into the peptide chain. This usually occurs because they come in 'triplets' so a single nucleotide change will have no effect on the protein being produced. Mutations are often linked to diseases or negative impacts but silent mutations can be extremely beneficial in creating genetic diversity among species in a population. Germ-line mutations are passed from the parent to the offspring. Scientists have predicted that people have approximately 5 to 10 deadly mutations in their genomes but this is essentially harmless because there is usually only one copy of a particular bad gene so diseases are unlikely. Silent mutations can also be produced by insertions or deletions, which cause a shift in the reading frame. Because silent mutations do not alter protein function they are often treated as though they are evolutionarily neutral. Many organisms are known to exhibit codon usage biases, suggesting that there is selection for the use of particular codons due to the need for translational stability. Transfer RNA (tRNA) availability is one of the reasons that silent mutations might not be as silent as conventionally believed. There is a different tRNA molecule for each codon. For example, there is a specific tRNA molecule for the codon UCU and another specific for the codon UCC, both of which code for the amino acid serine. In this instance, if there was a thousand times less UCC tRNA than UCU tRNA, then the incorporation of serine into a polypeptide chain would happen a thousand times more slowly when a mutation causes the codon to change from UCU to UCC. If amino acid transport to the ribosome is delayed, translation will be carried out at a much slower rate. This can result in lower expression of a particular gene containing that silent mutation if the mutation occurs within an exon. Additionally, if the ribosome has to wait too long to receive the amino acid, the ribosome could terminate translation prematurely. A nonsynonymous mutation that occurs at the genomic or transcriptional levels is one that results in an alteration to the amino acid sequence in the protein product. A protein's primary structure refers to its amino acid sequence. A substitution of one amino acid for another can impair protein function and tertiary structure, however its effects may be minimal or tolerated depending on how closely the properties of the amino acids involved in the swap correlate. The premature insertion of a stop codon, a nonsense mutation, can alter the primary structure of a protein. In this case, a truncated protein is produced. Protein function and folding is dependent on the position in which the stop codon was inserted and the amount and composition of the sequence lost. Conversely, silent mutations are mutations in which the amino acid sequence is not altered. Silent mutations lead to a change of one of the letters in the triplet code that represents a codon, but despite the single base change, the amino acid that is coded for remains unchanged or similar in biochemical properties. This is permitted by the degeneracy of the genetic code. Historically, silent mutations were thought to be of little to no significance. However, recent research suggests that such alterations to the triplet code do effect protein translation efficiency and protein folding and function. Furthermore, a change in primary structure is critical because the fully folded tertiary structure of a protein is dependent upon the primary structure.  The discovery was made throughout a series of experiments in the 1960s that discovered that reduced and denatured RNase in its unfolded form could refold into the native tertiary form.  The tertiary structure of a protein is a fully folded polypeptide chain with all hydrophobic R-groups folded into the interior of the protein to maximize entropy with interactions between secondary structures such as beta sheets and alpha helixes.  Since the structure of proteins determines its function, it is critical that a protein be folded correctly into its tertiary form so that the protein will function properly.  However, it is important to note that polypeptide chains may differ vastly in primary structure, but be very similar in tertiary structure and protein function.