Types of Gene Mutation
Let’s start by focusing on the types of mutations that can occur within our cells. First, we need to consider the nature of the mutation. A genetic mutation that occurs in sex cells is called a germline mutation. These mutations originate in meiosis and affect all cells of an individual, causing the mutation to be passed on to the next generation. If the mutation occurs in any other cell in the body, we call it a somatic mutation. These mutations originate in mitosis and only affect cells that descend from that single, mutated cell. These mutations are usually not passed on or inherited and are more commonly caused by environmental factors.
So how do we get mutations in the first place? There are three ways that mutations can occur. The first way, like described earlier is through inheriting the mutations. Another cause is through a spontaneous mutation, or de novo mutation, which occurs involuntarily and are not caused by mutagens. Instead, this type of mutation is caused by errors during DNA replication. On average, a person carries around 200 spontaneous mutations in their genome, which accounts for less than 1% of the 20,000 genes found in the human genome. Many of these mutations are recessive so not every generation will have these mutations passed along. Mutations that are caused by mutagens are called induced mutations. There are many different types of mutagens like alkylating agents, which remove a base from the DNA sequence; acridine dyes, which add or remove a base to/from the DNA sequence; x-ray radiation, which can break chromosomes; and UV radiation, which can create pyrimidine dimers between thymine or cytosine bases”. People can be exposed to these mutagens unintentionally, perhaps at their workplace, through overexposure to radiation at the hospital, or even sunlight.
Mutations can change the DNA sequence in a variety of ways. In a point mutation a single nucleotide is changed, which can lead to other mutations later on such as a missense or nonsense mutation. A missense mutation is a point mutation where one amino acid is replaced with another as a result of the single base change, which could lead to disease. A nonsense mutation is a point mutation that changes one amino acid to form a premature stop codon during transcription and translation. Depending on where the premature stop codon lands within the sequence, this can result in a truncated, or incomplete, protein. The third consequence of a point mutation could be a silent mutation meaning a base is changed, but the resulting amino acid stays the same, so it is almost as if it goes unnoticed.
Now, when we are trying to determine if a mutation will cause a change in the resulting protein, we have to consider whether or not it causes a frameshift. Since DNA is read in triplets, a frameshift is where bases are inserted, deleted, or duplicated to cause the reading frame to change. This frameshift will result in a mutation if the nucleotide change is not a multiple of three. For example, if seven bases are inserted into a gene, this will lead to a frameshift mutation because seven is not divisible by three.
The important thing to remember with gene mutations is that not all mutations impact protein function and therefore not all mutations cause disease. In fact, like I mentioned earlier, some mutations can be beneficial. For example, there is a beneficial mutation that affects certain people around the world known as G6PD-Mahidol 487A, which has been linked to malaria-resistance. Remember that silent mutations and frameshift changes that occur in multiples of three can go unnoticed. However, some changes are negative and there are ways that the cell deals with mutations so that they don’t cause harm. DNA repair is a mechanism within the cell that corrects for errors in DNA replication. Such errors are fairly uncommon, but the cell can try and repair itself by removing the damaged bit. If it can’t repair it, the damage will either cause the cell to die or result in cancer.
So, how do mutations actually cause disease? A good way to see this is by looking at cystic fibrosis. Cystic fibrosis is a disease where the affected person has trouble breathing, a lot of lung infections, and the lungs have an abnormal amount of mucus build-up. This occurs when the cystic fibrosis transmembrane regulator (CFTR) protein is missing an amino acid or some other change affects the conformation site of chloride channels. This changes the normal secretions of epithelial cells in the lungs and digestive tract to become thicker and stickier leading to the symptoms we just talked about. This is just one example of many, but thankfully, there are treatments for CF and other genetic diseases.
Before we go, let’s go over a quick review question to test your knowledge.
Which of the following is a type of gene mutation that we talked about today?
- Transient mutation
- Nonsense mutation
- Point mutation
The answer is both B and C. A nonsense mutation is a type of point mutation where one nucleotide is changed so that the codon codes to form a premature stop codon.
I hope this review was helpful. Thanks for watching, and happy studying!