Nonsense Mutation Definition
A nonsense mutation occurs when the sequence of nucleotides in DNA is changed in a way that prevents the normal sequence of amino acids in a protein. According to central dogma of biology, DNA is transposed into RNA, which is then translated into proteins. The protein is an amino acid sequence that confers a specific function to the cell. This role is determined by the properties and interactions of the amino acids in a sequence.
Each amino acid is designated by a codon, which is a series of three nucleotides. Approximately 21 amino acids can be designated using this system. Additionally, there are two other important signals, “START” and “STOP”. By using these signals, the ribosome can determine where to begin and where to finish assembling the protein. As a result of a nonsense mutation, the codon for an amino acid is changed into a “STOP” signal.
Because anything after the “STOP” signal is ignored, the protein structure is completely altered. As the ribosome snips off the incomplete protein, it continues on its way. Proteins may function and form differently without the remainder of the amino acid chain. It is possible to have three basic outcomes from a nonsense mutation.
Outcomes of a Nonsense Mutation
Deleterious
The vast majority of mutations are deleterious, meaning they reduce an organism’s fitness and reproductive success. If the mutation affected a functional protein, it would fall into this category. If the nonsense mutation was found in the DNA of an ion channel protein, what would happen? This protein would not be able to transport ions across the membrane if it was incomplete. As a result, the organism with the nonsense mutation would suffer harm.
Cystic fibrosis is a genetic disorder caused by a nonsense mutation which does exactly that. The protein affected by the nonsense mutation in cystic fibrosis is a regulator protein for ion channels. Without the ability to properly move ions, people with cystic fibrosis often have respiratory problems caused by a mucous buildup due to the unregulated ions in their system. Duchenne muscular dystrophy is another disease cause by a nonsense mutation, and there are many more examples.
Neutral
A neutral mutation occurs when the effects of the mutation go undetected. Imagine that the mutation is found right before the last amino acid in a protein. Further, this final amino acid is really unnecessary for the actual function of the protein within the cell. If this is the case, the nonsense mutation will produce no effect at all. The protein will continue to function, even without the final amino acid. In this case, nothing really changes for the organism.
Beneficial
The least common type of mutation is a beneficial mutation. This is a mutation in which the protein changes in such a way that it increases the fitness and reproductive success of the organism. However, it is extremely unlikely that a nonsense mutation will end up being beneficial. In only the rarest of circumstances, a nonsense mutation may be beneficial if changing the protein it affects somehow provides a benefit to the organism.
Imagine if the nonsense mutation affected a protein which inadvertently transports a toxin into cells. In an environment filled with the toxin, a dysfunctional protein might very well be the cure to being constantly bombarded with a toxin. If the protein no longer transported the toxin in, the cells wouldn’t need to worry about it.
In an even more unlikely circumstance, the nonsense mutation may completely alter the function of the protein. In this case, it might alter the protein to not transport the toxin, but rather destroy it or bind to it.
This could also be a case in which the nonsense mutation became beneficial. In the most extreme circumstance the nonsense mutation may take a protein used for one process, and create an entirely new active protein by cutting the other one in pieces. Much of this has to do with the exact protein affected and the resulting effects on the organism.
Nonsense Mutation Example
Point mutations
In this case, the original codon read “TTC”. This called for an mRNA with the codon “AAG”, which then produced a lysine in the amino acid chain. A nonsense mutation would change the first “T” to an “A”. This makes the first codon “ATC”. The corresponding mRNA segment, “UAG”, is a signal to the ribosome to stop the chain. Unlike any of the other mutations, this ends the chain entirely.
This is likely why nonsense mutations are often noticeable. It is unlikely that these mutations do not affect the resulting protein. Given that all of the amino acids play a role in a protein, dividing it at any point will likely change the way it interacts with the environment.
Even if only several amino acids are lost, these could be the crucial external amino acids which attach the protein to the cell membrane or help it interact with other cells.
FAQ’s
A nonsense mutation is a type of genetic mutation that occurs when a change in the DNA sequence of a gene results in a premature stop codon, or a stop signal that signals the end of protein synthesis. This can lead to the production of a truncated, non-functional protein.
Nonsense mutations are a type of point mutation, which involve a change in a single nucleotide of the DNA sequence. However, they differ from other types of point mutations such as missense mutations, which result in a different amino acid being incorporated into the protein, or silent mutations, which do not change the protein sequence.
A nonsense mutation can result in the production of a non-functional protein or the degradation of the mRNA transcript due to nonsense-mediated decay. This can lead to a range of genetic disorders, including cystic fibrosis, muscular dystrophy, and some forms of cancer.
Nonsense mutations can be detected through genetic testing, which involves sequencing the DNA of an individual to identify any mutations in a specific gene or set of genes. This can be used for diagnostic purposes or to identify carriers of genetic diseases.
While there is currently no cure for genetic disorders caused by nonsense mutations, there are some therapies under development that aim to restore protein function or bypass the nonsense mutation altogether. These include drugs that promote readthrough of the premature stop codon and gene editing technologies that aim to correct the underlying genetic mutation.