Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Mutations that occur at a single nucleotide are called point mutations. When point mutations occur within genes, the consequences can vary in severity depending on what happens to the encoded amino acid sequence. A silent mutation does not change the amino acid identity and will have no effect on an organism. A missense mutation changes a single amino acid, and the effects might be serious if the change alters the function of the protein. A nonsense mutation produces a stop codon that truncates the protein, likely rendering it nonfunctional. Frameshift mutations occur when one or more nucleotides are inserted into or deleted from a protein-coding DNA sequence, affecting all of the codons downstream of the location of the mutation.
The most drastic type of mutation, chromosomal alteration, changes the physical structure of a chromosome. Chromosomal alterations can include deletion, duplication, or inversion of large stretches of DNA within a single chromosome, or integration of a portion of a different chromosome. These mutations are typically far more serious than point mutations because they encompass many genes and regulatory elements. Chromosomal alterations can be detected by karyotyping the affected cell.
Mutations can occur in any cell, but only germline mutations—those present in egg and sperm cells—can be transmitted to offspring. For instance, hereditary diseases are a subtype of genetic disorder that are caused by deleterious germline mutations. They can be autosomal, occuring on chromosomes one through 22, or sex-linked, occurring on the X or Y chromosome. One example of a hereditary disease is cystic fibrosis (CF), a disease that primarily affects the lungs. It is caused by a deletion within the gene CFTR that removes a single amino acid from the CFTR protein. CF is an autosomal recessive disease, meaning that a person with one mutated copy of the gene and one normal copy will not develop the disease; other diseases, like Huntington’s disease, a neurodegenerative disorder, are autosomal dominant, meaning that only one mutated copy of the gene is necessary for the disease to develop.
Both somatic mutations—those that occur outside the germline—and germline mutations can arise spontaneously during DNA replication, but they can also be caused by exposure to radiation or chemicals in the environment. External factors that damage DNA and cause mutations are called mutagens. One well-characterized environmental mutagen is ultraviolet (UV) radiation. UV radiation carries more energy than visible light and damages DNA by breaking the bonds between base pairs, causing thymine bases on the same strand of DNA to pair with one another in characteristic thymine dimers. The sun is a natural source of UV radiation. The most damaging wavelengths, UV-C, are intercepted high in the atmosphere, but UV-A and UV-B rays reach the surface of the Earth. Artificial sources of UV exposure include tanning beds, which transmit primarily UV-A rays with smaller amounts of UV-B. Fortunately, cells have mechanisms to repair damaged DNA, but sometimes the damage is not repaired before cell division in rapidly-dividing cells, such as skin cells. If the DNA damage occurs in a genomic region that is important for regulation of cell growth and division, it can lead to cancer if it is not repaired.
