Mutation

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.

Contents

1 Types of mutations 2 Causes of mutation 3 Mutation and disease 4 See also 5 References 6 External links

Types of mutations

Basic types of mutations are:

• Small-scale mutations affecting one or a few nucleotides, including:
  • Point mutations, often caused by chemicals or malfunction of DNA replication, 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:
    • silent mutations: codes for the same amino acid, so has no effect
    • missense mutations: codes for a different amino acid
    • nonsense mutations: codes for a stop, which can truncate the protein
  • 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.

• Large-scale mutations in chromosomal structure, including:
  • Amplifications (or gene duplications) leading to multiple copies of chromosomal regions, increasing the dosage of the genes located within them
  • Deletions of large chromosomal regions, leading to loss of the genes within those regions
  • Mutations whose effect is to juxtapose previously separate pieces of DNA, potentially bringing together separate genes to form functionally distinct fusion genes (e.g. bcr-abl). These include:
    • Chromosomal translocations: attaching DNA from separate chromosomes
    • Interstitial deletions: removing regions of DNA from a single chromosome, thereby apposing previously distant genes (e.g. fig-ros)
    • Chromosomal inversions: switching the orientation of a segment of a chromosome, thereby apposing its ends to previously distant genes
  • Loss of heterozygosity: loss of one allele, either by a deletion or recombination event, in organisms which previously had two

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:

• Tautomerism
  • Keto ↔ Enol
  • Amino ↔ Imino
• Depurination 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))
  • Methylating agents (e.g. ethane methyl sulfonate (EMS))
  • 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.

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, creating partially 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 necessary 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.

See also

• Homeobox
• Macromutation
• Mutant

References

• 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.

External links

• The mutations chapter of the WikiBooks General Biology textbook
• EvoWiki: Mutation

Basic topics in evolutionary biology
Processes of evolution: macroevolution - microevolution - speciation
Mechanisms: selection - genetic drift - gene flow - mutation
Modes: anagenesis - catagenesis - cladogenesis
History: Charles Darwin - The Origin of Species - modern evolutionary synthesis
Subfields: population genetics - ecological genetics - human evolution - molecular evolution - phylogenetics - systematics - evo-devo
List of evolutionary biology topics | Timeline of evolution

See also: Mutation, 5-methylcytosine, Acid, Allele, Amino acid, Anagenesis, Base analog, Bcr-abl, Biology