Mutation: Meaning (information, definition, explanation, facts)

This article is about mutation in biology, for other meanings see: mutation (disambiguation).

Mutations (or mutagenesis, both words originating in the Latin word mutare, to change) are permanent, transmissible 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. In multicellular organisms, mutations can be subdivided into germline mutations, which can be passed on to progeny and somatic mutations, which 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 (C ↔ T, A ↔ G). 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). Point mutations are called silent, missense or nonsense mutations, depending on whether the erroneous codon codes for the same amino acid (silent), a different amino acid (missense) or a stop, which can truncate the protein (nonsense).
• 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.

Two classes of mutations are spontaneous mutations (naturally occurring) and induced mutations caused by mutagens.

Spontaneous mutations on the molecular level include:

• Tautomerism
  • Keto ↔ Enol
  • Amino ↔ Imino
• Deamination ap-site (loss of A or G); occurs 1000 times each day in mammals
• Deamination base analogs (C→Uracil or A→HX); occurs 100 times each day in mammals
• Transition
• Transversion
• Frameshift mutation (insertion or deletion on one strand), usually through a polymerase error when copying repeated sequences
• Oxidative damage caused by oxygen radicals

Induced mutations on the molecular level can be caused by:

• Chemicals
  • Nitrosoguanidine (NTG)
  • Base analogs (e.g. BrdU)
  • Simple chemicals (e.g. acids)
  • Alkylating agents (e.g. N-ethyl-N-nitrosourea (ENU))
  • Polycyclic hydrocarbons (e.g. benzpyrenes found in internal combustion engine exhaust)
  • DNA intercalating agents (e.g. ethidium bromide)
  • DNA crosslinker (e.g. platinum)
  • Oxygen radicals
• Radiation
  • Ultraviolet radiation
  • Ionizing radiation

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.