Lesson 4. What if regulation does not work – mutations

In this lesson we learn that mistakes called mutations sometimes occur in the DNA code. We learn that mutations create new versions of genes and that some mutations can be inherited.

Mutations are errors in the DNA

In the body, things are happening all the time at the cellular level: cells are dividing, tissues are regenerating, and DNA is telling the cells how to make a whole range of proteins. The function of DNA and the making of proteins is an incredibly precise and subtle process with different molecules having their own carefully regulated roles. It is amazing how precisely this machinery works.

But sometimes mistakes happen. So DNA replication also has ‘cops’ who, when they spot the wrong part, trigger the repair process.

If the transfer-RNA accidentally introduces the wrong amino acid, it can be replaced if the mistake is detected.

Sometimes the correction fails, or the error is not detected at all, and the recipe, the DNA sequence, is changed. A mutation has occurred.

Sites of mutations

A mutation can occur in a gene, its regulatory region or in a non-coding region of DNA. Depending on where the mutation occurs, its effect on the individual can be neutral, beneficial, harmful, or even life-threatening (lethal). A mutation in a gene can change the recipe for a protein, leading to the production of a different protein or preventing the production of a protein altogether. In the worst case, this can lead to the onset of a disease.

For example, a change in a gene that regulates embryonic development can be fatal for an individual because embryonic development is tightly regulated by genes, and a change in gene function can cause a wide range of structural and functional defects in the developing individual.

A cancer cell is formed when a mutation occurs in one of the genes that regulate cell division. The cell becomes a cancer cell, that, unlike normal cells, can divide indefinitely. Often such a cell is destroyed by cell self-destruction (apoptosis or programmed cell death) or other cells in the body may recognise it as foreign and destroy it, but this is not always the case.

Mutations are caused, for example, by ultraviolet light, ionising radiation, and various carcinogenic substances. Carcinogenicity is based on the ability to damage the DNA of a cell. Well-known carcinogens include tobacco smoke, asbestos, and alcohol. Mutations can also occur spontaneously when cells divide.

The different types of mutations

A mutation can be a change in a single base, called a point mutation (see illustrations above), or a change in several consecutive bases. Sometimes the mutation is so large that it changes the structure of the chromosome. Examples of structural changes are

  • Deletion, where a part of the chromosome is missing,
  • Substitution, where part of the chromosome is replaced by another part, and
  • Insertion, where an extra piece of DNA is attached to the chromosome.
Substitution (Illustration: Mäki and Mujunen 2018)

A mutation can also change the number of chromosomes. In humans, for example, Down syndrome is caused by an extra chromosome number 21 – there are three chromosomes number 21 instead of two. In Turner syndrome, a woman has only one X chromosome.

We all have mutations in our DNA

Mutations in germ cells can be inherited. However, somatic mutations only affect the individual and are not passed on to offspring. Germ cells are the cells that become sperm and eggs. Somatic cells are all cells that are not germ cells, sperm, or eggs. Almost all cells in the body are somatic cells.

Mutations occur in everyone. However, there are so many possible mutation sites in DNA base pairs that only two out of 100 million bases change every year. Therefore, the chance of a mutation occurring in a particular gene is very, very low.

In animals, for example, inherited mutations are known to cause eye diseases, metabolic disorders, and short tails.

The average human carries 250-300 functionally defective genes and 50-100 mutations known to cause inherited diseases*.

Because everyone inherits two copies of each gene, harmful inherited mutations are often hidden behind the normal gene variant. If an individual receives a defective gene from the father and a normal functioning gene from the mother, the mother’s gene is a functioning back-up.

*(Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA. A map of human genome variation from population-scale sequencing. Nature. 2010 Oct 28;467(7319):1061-73. doi: 10.1038/nature09534. Erratum in: Nature. 2011 May 26;473(7348):544.)

What have we learned?

  • Mutations are changes in the DNA base sequence. They can create new gene variants. In this way, mutations allow species to cope with changes in their environment.
  • Mutations in the germ cells can be inherited. Somatic mutations affect only the individual and are not passed on to offspring.
  • Most mutations are neutral and have no effect on the individual. Some mutations cause, for example, a disease or developmental disorder.
  • Because genes exist in duplicate, an individual often has a working copy of the gene.

Read more

Overview of Chromosomal Mutations, Types & Examples in humans by BioExplorer.net. (2023).

National Human Genome Research Institute explains what is a mutagen and also what is apoptosis.

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