Silent mutation
[3] 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.
[7] The set of three nucleotides almost always produce the same amino acid with a few exceptions like UGA which typically serves as the stop codon but can also encode tryptophan in mammalian mitochondria.
For example, if the codon AAA is altered to become AAG, the same amino acid – lysine – will be incorporated into the peptide chain.
[8][additional citation(s) needed] 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.
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.
[6] 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.
[11] The premature insertion of a stop codon, a nonsense mutation, can alter the primary structure of a protein.
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.
Secondary structure of proteins consists of interactions between the atoms of the backbone of a polypeptide chain, excluding the R-groups.
The other common type of secondary structure is the beta sheet, which displays a right-handed twist, can be parallel or anti-parallel depending on the direction of the direction of the bonded polypeptides, and consists of hydrogen bonds between the carbonyl and amino groups of the backbone of two polypeptide chains.
If the RNA molecule is highly stable, and the complementary bonds are strong and resistant to unpacking prior to translation, then the gene may be under expressed.
It has also been discovered that mRNA secondary structure is important for cell processes such as transcript stability and translation.
[17] If the oncoming ribosome pauses because of a knot in the RNA, then the polypeptide could potentially have enough time to fold into a non-native structure before the tRNA molecule can add another amino acid.
[18] Recent research suggests that silent mutations can have an effect on subsequent protein structure and activity.
Steffen Mueller at the Stony Brook University designed a live vaccine for polio in which the virus was engineered to have synonymous codons replace naturally occurring ones in the genome.
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.
A silent mutation in the multidrug resistance gene 1 (MDR1), 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.
For example, efavirenz and nelfinavir are two types of drugs that help decrease the HIV infection in a person's body.
Although, when the TT nucleotides in exon 26 are expressed the patient has a lower concentration of the virus but when the genotype morphs into CC or CT the infection is able to spread like normal leaving the MDR 1 gene almost defenseless.
[26] Looking at the molecular level, the reason why C3435T in exon 26 of MDR 1 gene is not silent is because of the pace at which the amino acids are being translated to proteins.
[24] The mutated codons have a higher risk of making a mistake when splicing introns out of the mRNA sequence leading to the wrong exons being produced.
