DNA encodes the fundamental blueprint for life, and any change to this sequence is known as a genetic mutation. These alterations can happen in any cell, but their impact depends on where and when they occur. Understanding these changes is central to modern biology, as they are the source of both variation and disease. The vast majority of DNA changes that occur throughout a person’s lifetime are somatic mutations, affecting only the individual in which they arise. This article focuses on how these acquired genetic changes manifest within the body’s non-reproductive cells.
Defining Somatic Mutations
A somatic mutation is any alteration to the DNA that takes place in a somatic cell—meaning any cell of the body except for reproductive cells (sperm or eggs). These changes occur after conception, throughout the life cycle, and are a normal part of aging. The term “somatic” is derived from the Greek word sōma, meaning “body,” which distinguishes these mutations from those that can be passed down to offspring.
When a somatic cell acquires a mutation, that alteration is passed down to all of its daughter cells when it divides through mitosis. This creates a lineage of cells within a specific tissue that all carry the same genetic change. Consequently, the effect of a somatic mutation is localized to the tissue where the original change occurred. The accumulation of these acquired mutations generates genetic variation within the individual, leading to genomic mosaicism.
Somatic Mutations Versus Germline Mutations
The distinction between somatic and germline mutations is based solely on the cell type in which the change originates, but this difference has profound consequences for heritability. A germline mutation occurs in the reproductive cells (egg or sperm) or is present immediately after fertilization. Because the resultant organism develops from that single mutated cell, the germline mutation is copied into every cell of the body.
Germline changes are inherited, meaning they can be passed from parent to child and affect future generations. Individuals carrying these mutations are born with the predisposition for a condition in all their cells, which is why germline mutations are associated with hereditary diseases. In contrast, somatic mutations are acquired during a person’s lifetime and are strictly non-heritable.
A person cannot pass a somatic mutation to their children because the mutation does not exist within their reproductive DNA. The impact remains confined to the individual’s body, affecting only the tissues derived from the cell where the initial alteration took place. Although both types represent a change in the DNA sequence, the difference lies in whether the change is inherited (germline) or acquired (somatic). Somatic mutation frequencies are often higher than germline frequencies, a disparity that may be linked to aging.
How Somatic Mutations Arise
Somatic mutations are generated through two main categories: spontaneous errors during normal cellular processes and damage caused by external environmental factors. The most common source of spontaneous change is the inherent fallibility of the cell’s machinery during DNA replication. As cells divide to grow or replace damaged tissue, the DNA polymerase enzyme can occasionally insert the wrong nucleotide base, leading to a mismatch.
Although the cell has robust repair mechanisms to correct these errors, some mistakes inevitably slip through and become permanent somatic mutations. These spontaneous changes are considered endogenous, arising from internal cellular activity, including the production of reactive oxygen species (free radicals) during normal metabolism. The rate of these replication errors increases as a person ages, leading to a greater accumulation of somatic changes.
The second major source is exposure to mutagens found in the external environment, which directly damage the DNA structure. Physical mutagens include high-energy radiation, such as ultraviolet (UV) light or X-rays, which can break DNA strands or cause adjacent DNA bases to chemically bond incorrectly. Chemical mutagens, like those found in tobacco smoke or industrial pollutants, can chemically modify the DNA bases, causing them to pair incorrectly during replication.
The Role of Somatic Mutations in Disease
The accumulation of somatic mutations over a lifetime is the primary driving force behind the development of most cancers. Cancer is fundamentally a disease of acquired somatic genetic change, where a single cell gains mutations that allow it to grow and divide uncontrollably. These mutations typically occur in specific categories of genes: proto-oncogenes and tumor suppressor genes.
A mutation in a proto-oncogene can turn it into an oncogene, acting like a gas pedal stuck in the “on” position and promoting uncontrolled cell growth. Conversely, a mutation in a tumor suppressor gene, such as TP53, removes a brake on cell division, eliminating mechanisms that normally halt growth or trigger cell death. The process usually requires the sequential accumulation of several somatic mutations in these different genes before a normal cell transforms into a malignant one.
Somatic mutations that happen very early in embryonic development can result in a condition called mosaicism. This means the person has two or more genetically distinct populations of cells originating from the same fertilized egg, with some cells carrying the mutation and others not. Depending on the gene affected and the proportion of cells involved, this early-onset somatic mutation can contribute to certain birth defects or predispose an individual to sporadic cancers later in life.