- This article is about mutation in biology, for other meanings see: mutation (disambiguation).
Mutations are permanent, sometimes transmissible (if the change is to a germ cell) changes to the genetic material (usually DNA or RNA) of a cell. Mutations can be caused by copying errors in the genetic material during cell division and by exposure to radiation, chemicals, or viruses, or can occur deliberately under cellular control during the processes such as meiosis or hypermutation. In multicellular organisms, mutations can be subdivided into germline mutations, which can be passed on to progeny and somatic mutations, which (when accidental) often lead to the malfunction or death of a cell and can cause cancer. Mutations are considered the driving force of evolution, where less favorable (or deleterious) mutations are removed from the gene pool by natural selection, while more favorable (or beneficial) ones tend to accumulate. Neutral mutations do not affect the organism's chances of survival in its natural environment and can accumulate over time, which might result in what is known as punctuated equilibrium; the modern interpretation of classic evolutionary theory.
It should be noted that, contrary to science fiction, the overwhelming majority of mutations have no real effect.
Types of mutations
Basic types of mutations are:
- Point mutations are usually caused by chemicals or malfunction of DNA replication and exchange a single nucleotide for another. Most common is the transition that exchanges a purine for a purine or a pyrimidine for a pyrimidine (A ↔ G, C ↔ T). A transition can be caused by nitrous acid, base mispairing, or mutagenic base analogs such as 5-bromo-2-deoxyuridine (BrdU). Less common is a transversion, which exchanges a purine for a pyrimidine or a pyrimidine for a purine (C/T ↔ A/G). A point mutation can be reversed by another point mutation, in which the nucleotide is changed back to its original state (true reversion) or by second-site reversion (a complementary mutation elsewhere that results in regained gene functionality). There are three kinds of point mutations, depending upon what the erroneous codon codes for:
- Insertions add one or more extra nucleotides into the DNA. They are usually caused by transposable elements, or errors during replication of repeating elements (e.g. AT repeats). Most insertions in a gene can cause a shift in the reading frame (frameshift) or alter splicing of the mRNA, both of which can significantly alter the gene product. Insertions can be reverted by excision of the transposable element.
- Deletions remove one or more nucleotides from the DNA. Like insertions, these mutations can alter the reading frame of the gene. They are irreversible.
Causes of mutation
Two classes of mutations are spontaneous mutations (naturally occurring) and induced mutations caused by mutagens.
Spontaneous mutations on the molecular level include:
Induced mutations on the molecular level can be caused by:
DNA has so-called hotspots, where mutations occur up to 100 times more frequently than the normal mutation rate. A hotspot can be at an unusual base, e.g., 5-methylcytosine.
Mutation rates also vary across species. Evolutionary biologists have theorized that higher mutation rates are beneficial in some situations, because they allow organisms to evolve and therefore adapt faster to their environments.
Mutation and disease
Spontaneous, induced and hereditary mutations can cause human disease. Mutation can affect human health, causing disease by disrupting a cell's normal biological functions.
Changes in the DNA caused by mutation can cause errors in protein sequence, createing pratially or non-functional proteins. To function correctly, each cell depends on thousands of proteins to function in the right places at the right times. Sometimes, gene mutations prevent one or more of these proteins from functioning correctly, causing malfunction or loss of a necesary protein. When a mutation alters a protein that plays a critical role in the body, a medical condition can result. A condition caused by mutations in one or more genes is called a genetic disorder.
Often, gene mutations that could cause a genetic disorder are repaired by the cell's DNA repair enzymes before the gene is expressed (makes a protein). Each cell has a number of pathways through which enzymes recognize and repair mistakes in DNA. Because DNA can be damaged or mutated in many ways, the process of DNA repair is an important way in which the body protects itself from disease.
- Maki H. 2002. Origins of spontaneous mutations: specificity and directionality of base-substitution, frameshift, and sequence-substitution mutageneses. Annual Review of Genetics 36:279-303.