Harmful Mutations

Mutations are changes within our genetic code due to random editing errors during our gene expression. The X-men in the marvel universe are fictional examples of what mutations look like in humans. In reality, mutations are all around us. People with blue and green eyes get their eye colour from mutations. The average human may not have wolverine claws, telekinesis, or superhuman strength, but they will possess a wide range of mutations in their genome that make them unique. Most mutations are harmless; however, some mutations can cause serious harm to the affected organism. In this article, we will be discussing many harmful mutations and their effects on humans.

What are harmful mutations?

Harmful mutations are variations in an organism's genetic code that cause harmful changes in gene expression. Harmful mutations arise from exposure to harmful chemicals, viruses, traumatic injury, radiation, UV light, or hereditarily. Such mutations can be caused in two ways: induced or spontaneous.¹

Induced mutations are caused by exposure to harmful things in the environment, such as chemicals, UV light, and radiation, while spontaneous mutations occur randomly within the body due to natural reactions that take place within the body. The majority of spontaneous mutations are harmless, though a minority can be quite harmful to the organism. Mutations can be point mutations, frameshift mutations, substitution mutations, nonsense mutations, missense mutations, addition mutations, or subtraction mutations. See the point mutations article for more discussion on these types of mutations.

Harmless mutations are usually not expressed, meaning they do not alter the organism's gene expression. These types of mutations are known as silent mutations. A silent mutation is a type of substitution or point mutation where the organism's gene expression is not affected. Typically silent mutations arise when a base pair is changed, but the new codon still codes for the same amino acid as the original codon.

Examples of harmful mutations

Point mutations are usually harmless if they are silent mutations. Missense and nonsense point mutations, however, can cause serious disease because these mutations can change the codon completely, where the new codon codes for an entirely different amino acid.² This phenomenon is seen in the case of sickle cell anaemia which is a debilitating disease characterized by poor blood flow to bodily organs and chronic pain.⁵

Sickle cell anaemia is caused by a missense point mutation in the haemoglobin gene. Within the normal haemoglobin gene, the codon GAA codes for glutamic acid leading to a healthy round haemoglobin A molecule. However, when the sickle cell point mutation is present, GAA is converted to GUA.⁵ GUA codes for the amino acid valine, which produces haemoglobin S a sticky sickle-shaped haemoglobin molecule that causes the organism's red blood cells to stick together, drastically reducing blood flow to areas of the body. ⁵

People with sickle cell disease inherit this point mutation from family members as the mutation is carried on the DNA level. The mutated gene is a recessive gene which means that the offspring must have both mutated genes to have the full sickle cell anaemia disorder. Offspring with only one mutated gene still have sickle cells in their system however, only a portion of their cells are misshapen, while their reminding cells are fully healthy.⁵

The most common harmful mutations are substitution point mutations, as seen in sickle cell anaemia. These mutations result when one base is replaced by another base. There are two types of substitution mutations: transitions and transversions.¹ Transition substitutions occur when a purine or pyrimidine is replaced by a base of the same kind.¹ For example, a purine such as adenine may be replaced by another purine such as guanine. A transversion substitution on the other hand occurs when a purine is replaced by a pyrimidine.¹ For example, the purine adenine may be replaced by the pyrimidine cytosine.

Other types of harmful mutations include nonsense and frameshift mutations. Nonsense mutations result when an amino acid coding codon is substituted for a stop codon.² Nonsense mutations can be very harmful to organisms because it prevents the entire gene from being transcribed due to a premature stop codon being inserted into the gene. Nonsense mutations can cause rare genetic diseases such as Duchenne muscular dystrophy, cystic fibrosis, and various cancers and neurological disorders.² We will discuss some of these specific diseases in a later section.

Frameshift mutations are arguably the most harmful type of mutation because they result in a shift in the gene reading frame.¹ Frameshift mutations are caused by random insertions or deletions of bases in the DNA. These mutations have the potential to change every codon in a genetic sequence or create a premature stop codon. Let's take a look at an example.

See Figure 2 for an illustration of the various types of point mutations.

Harmful effects of genetic mutations

As previously mentioned, genetic mutations have many harmful effects on organisms. Genetic mutations can cause various rare diseases such as muscular dystrophy, Huntington's disease, cancer, and much more.² Also mutations that occur during fetal development can cause physical disabilities such as microcephaly, cleft lips, spina bifida, and other congenital disorders. It is arguable that mutations in the fetal brain cause disorders such as Autism, ADHD, and other mental disorders, though there are no conclusive research findings.

Negative effects of mutation

As previously mentioned, mutations can have negative effects on the affected organism, such as disease, deformity, and even death. Mutations can also affect a person in ways that are not obvious. For example, pathogens such as viruses infect host organisms and attempt to take over the host's cells. Once your body is infected with a virus, your immune system works hard to kill the virus to prevent it from infecting any more of your healthy cells. Once the virus is dead, your body deploys antibodies specific to antigens on the virus to prevent it from entering your cell if you were to get infected again. The reason why we are always getting sick from the same virus is that viruses have the ability to evolve.

Viruses are just strings of genetic code that hijack your cells in order to reproduce. Just like your cells need to transcribe DNA in your to reproduce, viruses too require transcriptional machinery to do so. However, viruses do not have their own translational machinery, which is why they target host cells. Since the virus is made up of genetic material, it has the ability to mutate and develop changes in its protein structure and function. these changes allow viruses to evade antibodies and mechanisms placed by your immune system, which is why we continue to get sick from the same virus and why we need to get vaccinated every year. Sometimes we need to get vaccinated more than once a year in the case of highly mutagenic viruses like COVID-19.

List of harmful mutations

We have already discussed how harmful mutations can be to an organism. Let's move on to discussing specific examples of harmful mutations. In a previous section, we discussed that mutations can cause many diseases such as cancer and cystic fibrosis. These diseases can be very debilitating to the affected organism, as their quality of life and life expectancy will suffer.

In the case of cystic fibrosis, it is caused by mutations in the gene that produces the cystic fibrosis transmembrane conductance regulator protein (CFTR).⁴ The most common mutation associated with CF is the deletion of a phenylalanine at position 508. This mutation leads to lung disease due to the build-up of mucus.