DNA Mutations

What you’ll learn to do: Recognize the impact of DNA mutations

A mutation is a permanent alteration in the DNA sequence that makes up a gene; that is, the sequence differs from what is found in most people. Mutations range in size; they can affect anywhere from a single DNA building block (base pair) to a large segment of a chromosome that includes multiple genes. Gene mutations can be classified in two major ways:

  • Hereditary mutations are inherited from a parent and are present throughout a person’s life in virtually every cell in the body.
  • Acquired (or somatic) mutations occur at some time during a person’s life and are present only in certain cells, not in every cell in the body.

Mutations can impact an organism in both negative and positive ways—and sometimes a genetic mutation doesn’t impact the organism at all!

Learning Outcomes

  • Understand what a mutation is and how one generally occurs
  • Identify the major types of DNA mutations

What is a Mutation?

Over a lifetime, our DNA can undergo changes or mutations in the sequence of bases: A, C, G and T. This results in changes in the proteins that are made. This can be a bad or a good thing.

A mutation is a change that occurs in our DNA sequence, either due to mistakes when the DNA is copied or as the result of environmental factors such as UV light and cigarette smoke. Mutations can occur during DNA replication if errors are made and not corrected in time. Mutations can also occur as the result of exposure to environmental factors such as smoking, sunlight and radiation. Often cells can recognize any potentially mutation-causing damage and repair it before it becomes a fixed mutation.

Mutations contribute to genetic variation within species. Mutations can also be inherited, particularly if they occur in a germ cell (reproductive egg or sperm). Mutations that have a positive effect are more likely to be continually passed on. For example, the disorder sickle cell anaemia is caused by a mutation in the gene that instructs the building of a protein called hemoglobin. This causes the red blood cells to become an abnormal, rigid, sickle shape. However, in African populations, having this mutation also protects against malaria.

However, mutation can also disrupt normal gene activity and cause diseases, like cancer. Cancer is the most common human genetic disease; it is caused by mutations occurring in a number of growth-controlling genes. Sometimes faulty, cancer-causing genes can exist from birth, increasing a person’s chance of getting cancer.

An example of a point mutation. The original sequence reads TAACTGC. . . The strand with the point mutation reads TAACCGC. . . A single thymine has been turned into a cytosine.

Figure 1. An illustration to show an example of a DNA mutation. Image credit: Genome Research Limited

Major Types of Mutations

Photo shows a person with mottled skin lesions that result from xermoderma pigmentosa.

Figure 2. Xeroderma pigmentosa is a condition in which thymine dimerization from exposure to UV is not repaired. Exposure to sunlight results in skin lesions. (credit: James Halpern et al.)

A well-studied example of a mutation is seen in people suffering from xeroderma pigmentosa (Figure 2). Affected individuals have skin that is highly sensitive to UV rays from the sun.

When individuals are exposed to UV, pyrimidine dimers, especially those of thymine, are formed; people with xeroderma pigmentosa are not able to repair the damage. These are not repaired because of a defect in the nucleotide excision repair enzymes, whereas in normal individuals, the thymine dimers are excised and the defect is corrected. The thymine dimers distort the structure of the DNA double helix, and this may cause problems during DNA replication. People with xeroderma pigmentosa may have a higher risk of contracting skin cancer than those who don’t have the condition.

Errors during DNA replication are not the only reason why mutations arise in DNA. Mutations, variations in the nucleotide sequence of a genome, can also occur because of damage to DNA. Such mutations may be of two types: induced or spontaneous. Induced mutations are those that result from an exposure to chemicals, UV rays, x-rays, or some other environmental agent. Spontaneous mutations occur without any exposure to any environmental agent; they are a result of natural reactions taking place within the body.

Mutations may have a wide range of effects. Some mutations have no impact on an organism; these are known as silent mutations. Point mutations are those mutations that affect a single base pair. The most common nucleotide mutations are substitutions, in which one base is replaced by another. These can be of two types, either transitions or transversions. Transition substitution refers to a purine or pyrimidine being replaced by a base of the same kind; for example, a purine such as adenine may be replaced by the purine guanine. Transversion substitution refers to a purine being replaced by a pyrimidine, or vice versa; for example, cytosine, a pyrimidine, is replaced by adenine, a purine. Mutations can also be the result of the addition of a base, known as an insertion, or the removal of a base, also known as deletion. Sometimes a piece of DNA from one chromosome may get moved to another chromosome or to another region of the same chromosome; this is also known as translocation.

Mutations in repair genes have been known to cause cancer. Many mutated repair genes have been implicated in certain forms of pancreatic cancer, colon cancer, and colorectal cancer. Mutations can affect either somatic cells or germ cells. If many mutations accumulate in a somatic cell, they may lead to problems such as the uncontrolled cell division observed in cancer. If a mutation takes place in germ cells, the mutation will be passed on to the next generation, as in the case of hemophilia and xeroderma pigmentosa.

The Causes of Genetic Mutations

In Summary: Major Types of Mutations

DNA polymerase can make mistakes while adding nucleotides. Most mistakes are corrected, but if they are not, they may result in a mutation defined as a permanent change in the DNA sequence. Mutations can be of many types, such as substitution, deletion, insertion, and translocation. Mutations in repair genes may lead to serious consequences such as cancer. Mutations can be induced or may occur spontaneously.

Check Your Understanding

Answer the question(s) below to see how well you understand the topics covered in the previous section. This short quiz does not count toward your grade in the class, and you can retake it an unlimited number of times.

Use this quiz to check your understanding and decide whether to (1) study the previous section further or (2) move on to the next section.