Nonsense Mutation Definition
A nonsense mutation occurs when the sequence of nucleotides in DNA is changed in a way that stops the normal sequence of amino acids in the final protein. In central dogma of biology, DNA is transposed into RNA, which is then translated into a protein. The protein is a particular sequence of amino acids which confers a particular function onto the cell. The sequence of amino acids determines this role by the properties they contain and the ways they interact.
In the DNA, each amino acid is designated by a series of three nucleotides, called a codon. There are around 21 amino acids which can be designated by this system. There are also two other important signals, “START” and “STOP”. These signals allow the ribosome assembling the protein to know where to begin, and where to end. A nonsense mutation changes the codon for an amino acid into the codon for a “STOP” signal.
This completely changes the structure of the protein, because anything after the “STOP” signal is ignored. The ribosome snips off the incomplete protein and goes on its way. Without the remainder of the amino acid chain, the protein may function and form completely differently than before. A nonsense mutation can have three basic outcomes.
Outcomes of a Nonsense Mutation
The vast majority of mutations are deleterious, meaning they cause a decrease in the overall fitness and reproductive success of the organism. A nonsense mutation would fall into this category if the mutation affected an important functional protein. Imagine if the nonsense mutation was found in the DNA which coded for an ion channel protein. If this protein was incomplete, it could not function to properly transport ions across the membrane. This would be deleterious to the organism with the nonsense mutation.
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.
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.
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
Below is a chart of several point mutations, or mutations of a single nucleotide. A nonsense mutation can be seen in the middle.
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.