What Is a Human Mutation? Causes, Types, and Impact

A human mutation is a change in the DNA sequence that provides the instructions for our bodies. These alterations can range from single-letter changes to large-scale rearrangements of our genetic code. While some changes lead to disease, many have no effect, and some can be beneficial. Cellular machinery can often recognize and repair these changes before they become permanent.

The Blueprint Altered: Types of Genetic Mutations

A point mutation affects a single location in the DNA sequence, where one DNA base is swapped for another. A missense mutation is a type of point mutation that results in a different amino acid being incorporated into a protein, which can alter its function. An example is sickle cell anemia, where a single substitution in the beta-hemoglobin gene changes one amino acid in the resulting protein.

Another type of point mutation is a nonsense mutation, which changes an amino-acid-coding codon to a “stop” codon. This signals the cell to stop building the protein prematurely, resulting in an incomplete and likely non-functional protein. Conversely, a silent mutation is a base substitution that, due to the redundancy of the genetic code, does not change the amino acid sequence of the protein and typically has no effect.

Larger-scale changes, known as frameshift mutations, occur when nucleotides are added (insertion) or removed (deletion) from the DNA sequence. Since DNA is “read” in three-base codons, these insertions or deletions can shift the entire reading frame, causing all subsequent codons to be misinterpreted. This often leads to the creation of a completely nonfunctional protein. Cystic fibrosis is an example of a disease that can be caused by the deletion of just three DNA bases, leading to a faulty protein.

Mutations can also happen at the chromosomal level, affecting large segments of DNA. These can be numerical, where an individual has an abnormal number of chromosomes, a condition known as aneuploidy. Structural abnormalities involve changes to the structure of a chromosome and include:

• Deletions, where a segment is lost.
• Duplications, where a segment is repeated.
• Inversions, where a segment is flipped and reinserted.
• Translocations, where a piece of one chromosome breaks off and attaches to another.

Origins of Change: How Mutations Arise

Mutations can arise from two primary sources: spontaneously from natural processes or induced by external factors. Spontaneous mutations often result from errors made during DNA replication, the process by which a cell copies its DNA. While this process is remarkably accurate, mistakes can happen, and chemical changes can also spontaneously occur in DNA.

Induced mutations are caused by exposure to environmental agents known as mutagens. These can be physical, such as ultraviolet (UV) radiation from the sun and ionizing radiation like X-rays. This radiation can damage DNA, causing breaks or other alterations.

Chemical mutagens are another source of induced mutations, including components of tobacco smoke and industrial pollutants. Some chemicals can directly damage DNA, while others can insert themselves between the DNA bases, causing errors during replication. Certain viruses are also biological mutagens, integrating their genetic material into the host’s DNA and disrupting gene function.

Passing the Torch: Inheritance and Somatic vs. Germline Mutations

Mutations are categorized as either somatic or germline, depending on the cell type in which they occur. Somatic mutations occur in the body’s non-reproductive cells, such as skin or muscle cells. These mutations will only affect the individual in which they arise and are not passed on to their children.

A somatic mutation is passed down to all subsequent cells that develop from the mutated cell. This can contribute to the development of some forms of cancer or lead to a condition called mosaicism, where an individual has populations of cells with different genetic makeups. These mutations are often caused by environmental factors encountered during a person’s lifetime.

In contrast, germline mutations occur in the reproductive cells—the egg and sperm. These are the mutations that can be inherited by offspring. When a germline mutation is passed on, it will be present in virtually every cell of the child’s body. This is the basis for many hereditary diseases.

The Double-Edged Sword: Impact of Mutations on Human Health and Evolution

Harmful mutations can lead to genetic disorders by producing a non-functional or improperly functioning protein. For example, Huntington’s disease results from an expansion of a repeating DNA sequence in the HTT gene. Other genetic disorders are caused by different types of mutations that create faulty proteins.

Many mutations are neutral, having no discernible effect on an individual’s health or ability to survive. These can occur in non-coding regions of DNA or may result in a change to the protein sequence that doesn’t alter its function. Most mutations that happen in our cells fall into this category or are repaired quickly.

Rarely, a mutation can be beneficial, providing a survival or reproductive advantage. A classic example is the mutation that allows some adults to digest lactose. Another well-studied beneficial mutation is in the CCR5 gene, which can provide resistance to HIV infection. These advantageous mutations are the raw material for evolution, as they introduce new traits into a population that natural selection can act upon.