In biology, mutations are permanent, sometimes transmissible (if the change is to a germ cell) changes to the genetic material (usually DNA or RNA). 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 cannot be transmitted to progreny. Mutations, 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 are defined as mutations whose effects do not influence the fitness of either the species or the individuals who make up the species. These can accumulate over time. Contrary to tales of science fiction, the overwhelming majority of mutations have no significant effect. Visible effects are especially rare, since DNA repair is able to reverse most changes before they become permanent mutations. Main articles: Life The most salient example of biological universality is that all living things share a common carbon-based biochemistry and in particular pass on their characteristics via genetic material, which is based on nucleic acids such as DNA and which uses a common genetic code with only minor... A germ cell is a kind of cell that is part of the germline, and is involved in the reproduction of organisms. ... Genetic material is the material used to store genetic information for a living organism. ... Space-filling model of a section of DNA molecule Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions specifying the biological development of all cellular forms of life (and most viruses). ... Ribonucleic acid (RNA) is a nucleic acid polymer consisting of covalently bound nucleotides. ... Cell division is the process by which a cell (called the parent cell) divides into two cells (called daughter cells). ... Radiation has a variety of different meanings. ... A common alternate meaning of virus is computer virus. ... In biology, meiosis is the process that transforms one diploid cell into four haploid cells in eukaryotes in order to redistribute the diploids cells genome. ... This article needs to be cleaned up to conform to a higher standard of quality. ... Germline is a word used in biology and genetics. ... Somatic means to refer to the body. ... When normal cells are damaged beyond repair, they are eliminated by apoptosis. ... A speculatively rooted phylogenetic tree of all living things, based on rRNA gene data, showing the separation of the three domains, bacteria, archaea, and eukaryotes, as described initially by Carl Woese. ... Natural selection is the name Charles Darwin gave to the principal process through which new species emerge, or evolve. ... The neutral theory of molecular evolution (also, simply the neutral theory of evolution) is an influential theory that was introduced with provocative effect by Motoo Kimura in the late 1960s and early 1970s. ... Science fiction is a form of speculative fiction principally dealing with the impact of imagined science and technology, or both, upon society and persons as individuals. ... DNA damage resulting in multiple broken chromosomes DNA repair is a process constantly operating in cells; it is essential to survival because it protects the genome from damage. ...

Structural classification

The DNA sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health, depending on where they occur and whether they alter the function of essential proteins. Structurally, mutations can be classified as:

• 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 (A ↔ G) or a pyrimidine for a pyrimidine, (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). These changes are classified as transitions or transversions. An example of a transversion is adenine being converted into a cytosine. There are also many other examples that can be found. Point mutations that occur wihtin the protein coding region of a gene may be classified into three kinds, depending upon what the erroneous codon codes for:
    • silent mutations: codes for the same amino acid
    • 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). Insertions in the coding region a gene may alter splicing of the mRNA, or cause a shift in the reading frame (frameshift), 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.

A point mutation, or substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide. ... A nucleotide is a monomer or the structural unit of nucleotide chains forming nucleic acids as RNA and DNA. A nucleotide consists of a heterocyclic nucleobase, a pentose sugar (ribose or deoxiribose), and a phosphate or polyphosphate group. ... Purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. ... Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring. ... Nitrous acid weak monobasic acid known only in solution and in the form of nitrite salts. ... Also known as 5-bromo-2-deoxyuridine, this chemical is a base analog of thymidine, with the thymine substituted by bromouracil. ... Silent mutations or synonymous mutations are DNA mutations that, although they alter a particular codon, they do not alter the final amino acid, and hence do not affect the final protein. ... In chemistry, an amino acid is any molecule that contains both amino and carboxylic acid functional groups. ... Missense mutations or nonsynonymous mutations are types of point mutations where a nucleotide is changed which results in a different amino acid. ... In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon (also called a nonsense codon) in the transcribed mRNA, and possibly a truncated (and often nonfunctional) protein product. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... One or more bases added to DNA base sequence, alters the framing of codons Category: Science stubs ... Transposons are sequences of DNA that can move around to different positions within the genome of a single cell, a process called Transposition. ... Ribonucleic acid (RNA) is a nucleic acid polymer consisting of covalently bound nucleotides. ... In biology, a reading frame is a contiguous and non-overlapping set of three-nucleotide codons in DNA or RNA. There are 3 possible reading frames in a strand. ... Framing error is the following: Generally, a framing error is the result of reading a string of symbols which are grouped in blocks starting at the wrong point. ... Transposons are sequences of DNA that can move around to different positions within the genome of a single cell, a process called Transposition. ... A gene deletion, or deletion mutation is a genetic mutation in which a part of a chromosome or a sequence of DNA is missing. ... In biology, a reading frame is a contiguous and non-overlapping set of three-nucleotide codons in DNA or RNA. There are 3 possible reading frames in a strand. ... Figure 1: Chromosome. ... Schematic of a region of a chromosome before and after a duplication event Gene duplication occurs when an error in DNA replication leads to the duplication of a region of DNA containing a (generally functional) gene. ... A gene deletion, or deletion mutation is a genetic mutation in which a part of a chromosome or a sequence of DNA is missing. ... Fusion gene - Wikipedia /**/ @import /skins/monobook/IE50Fixes. ... A karyotype showing translocation 9;22 Philadelphia chromosome or Philadelphia translocation is a specific genetic, chromosomal abnormality that is associated with chronic myelogenous leukemia (CML). ... Chromosomal translocation of the 4th and 20th chromosome. ... An inversion is a chromosome rearrangement in which a segment of a chromosome is reversed end to end. ... Loss of heterozygosity in a cell represents the loss of a single parents contribution to part of its genome. ... An allele is any one of a number of viable DNA codings of the same gene (sometimes the term refers to a non-gene sequence) occupying a given locus (position) on a chromosome. ... Recombination usually denotes a genetic event that occurs during the formation of sperm and egg cells (especially in areas of study of biology topics). ...

Functional classification

Mutations in genes can be classified according to how they change the function or expression of the gene product. The following terms describe mutations that affect the gene product directly:

• Loss-of-function mutations are the result of gene product having less or no function. When the allele has a complete loss of function (null allele) it is often called an amorphic mutation. Phenotypes associated with such mutations are most often recessive. Exceptions are when the organism is haploid, or when the reduced dosage of normal gene product is not enough for normal phenotype (this is called haploinsufficiency).
• Gain-of-function mutations change the gene product such that it gains a new and abnormal function. These mutations usually have dominant phenotypes.
• Dominant negative mutations (also called antimorphic mutations) have an altered gene product that acts antagonistically to the wild-type allele. These mutations usually result in an altered molecular function (often inactive) and are characterised by a dominant or semi-dominant phenotype.
• Lethal mutations are mutations that lead to a phenotype incapable of effective reproduction.
• Conditional mutation is a mutation that has wild-type phenotype under certain environmental conditions and a mutant phenotype under certain selective conditions. Conditional mutations may also be lethal under certain conditions.

Some characterizations also include mutations that affect expression of a gene: A null allele is an allele with the effect of either absence of the gene product at the molecular level, or the absence of function at the phenotypic level. ... In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ... Haploid (meaning simple in Greek) cells have only one copy of each chromosome. ... Haploinsufficiency occurs when a diploid organism only has a single copy of a wild-type gene, with the other copy being inactivated by hereditary mutation or another mechanism. ... In genetics, the term dominant gene refers to the allele that causes a phenotype that is seen in a heterozygous genotype. ... In genetics, the term dominant gene refers to the allele that causes a phenotype that is seen in a heterozygous genotype. ... It has been suggested that this article or section be merged with dominance relationship. ...

• Hypomorphic mutations are mutations that cause reduced function of the gene product, or a negative change in expression of the gene.

• Hypermorphic mutations are the opposite of hypomorphic mutations; they cause increased activity or expression of the gene product.

• Neomorphic mutations cause a novel molecular function or expression of the gene product.

The following types of mutations are classified according to their phenotypic results:

• Morphological mutations usually affect the outward appearance of an individual. Mutations can change the height of a plant or change it from smooth to rough seeds.
• Biochemical mutations result in lesions stopping the enzymatic pathway. Often, morphological mutants are the direct result of a mutation due to the enzymatic pathway.

Causes of mutation

Two classes of mutations are spontaneous mutations (molecular decay) and induced mutations caused by mutagens. In biology, a mutagen (Latin, literally origin of change) is an agent that changes the genetic information (usually DNA) of an organism and thus increases the number of mutations above the natural background level. ...

Spontaneous mutations on the molecular level include:

• Tautomerism - A base is changed by the repositioning of a hydrogen atom.
• Depurination - Loss of a purine base (A or G).
• Deamination - Changes a normal base to an atypical base; C → U, (which can be corrected by DNA repair mechanisms), or spontaneous deanimation of 5-methycytosine (unreparable), or A → HX (hypoxanthine).
• Transition - A purine changes to another purine, or a pyrimidine to a pyrimidine.
• Transversion - A purine becomes a pyrimidine, or vice versa.

Induced mutations on the molecular level can be caused by: Tautomers are organic compounds that are interconvertible by a chemical reaction called tautomerization. ... DNA alteration in which the hydrolysis of a purine base (A or G) from the deoxyribose-phosphate backbone occur. ... Deamination is the removal of an amine group from a molecule. ...

• Chemicals
  • Nitrosoguanidine (NTG)
  • Base analogs (e.g. BrdU)
  • Simple chemicals (e.g. acids)
  • Alkylating agents (e.g. N-ethyl-N-nitrosourea (ENU)) These agents can mutate both replicating and non-replicating DNA. In contrast, a base analog can only mutate the DNA When the analog is incorporated in replicating the DNA. Each of these classes of chemical mutagens has certain effects that then lead to transitions, transversions, or deletions.
  • 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)
  • Oxidative damage caused by 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. A base analog is a chemical that can substitute a normal nucleobase in nucleic acids. ... Also known as 5-bromo-2-deoxyuridine, this chemical is a base analog of thymidine, with the thymine substituted by bromouracil. ... An acid (from Arabic Azait meaning oil, often represented by the generic formula AH) is typically a water-soluble, sour-tasting chemical compound. ... ENU, also known as N-ethyl-N-nitrosourea (chemical formula C3H6N3O2), is a highly potent mutagen in mice. ... Ethyl methyl sulfonate (CH3SO3CH2CH3) and ethyl ethane sulfonate (CH3CH2SO3CH2CH3) are ethylating of the purine ring and ends with the hydrolysis of the purine deoxyribose bond. ... In chemistry, a hydrocarbon is a cleaning solution consisting only of carbon (C) and hydrogen (H). ... Benzopyrene, C20H12, is a five-ring polycyclic aromatic hydrocarbon that is mutagenic and highly carcinogenic. ... A colorized automobile engine The internal combustion engine is a heat engine in which combustion occurs in a confined space called a combustion chamber. ... The word exhaust can mean:- A verb meaning tire out, as in After the long gallop, his horse was exhausted. ... Ethidium bromide (EtBr) is an intercalating agent commonly used as a nucleic acid stain in molecular biology laboratories for techniques such as agarose gel electrophoresis. ... General Name, Symbol, Number platinum, Pt, 78 Chemical series transition metals Group, Period, Block 10, 6, d Appearance grayish white Atomic mass 195. ... General Name, Symbol, Number oxygen, O, 8 Chemical series Chalcogens Group, Period, Block 16, 2, p Appearance colorless Atomic mass 15. ... Radical is derived from the Latin word radix, which means root. In various fields of endeavor, it can mean: Sciences in chemistry, either an atom or molecule with at least one unpaired electron, or a group of atoms, charged or uncharged, that act as a single entity in reaction. ... Ultraviolet (UV) radiation is electromagnetic radiation of a wavelength shorter than that of the visible region, but longer than that of soft X-rays. ... Ionizing radiation is a type of particle radiation in which an individual particle (for example, a photon, electron, or helium nucleus) carries enough energy to ionize an atom or molecule (that is, to completely remove an electron from its orbit). ... 5-methylcytosine is the methylated form of cytosine. ...

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 more quickly to their environments. For example, repeated exposure of bacteria to antibiotics, and selection of resistant mutants, can result in the selection of bacteria that have a much higher mutation rate than the original population (mutator strains). In genetics, mutation rates are the speed at which mutations in an organism or a species take place. ... A mutator genotype is a genotype with an elevated rate of mutation. ...

Mutation and disease

Changes in DNA caused by mutation can cause errors in protein sequence, creating partially or completely non-functional proteins. To function correctly, each cell depends on thousands of proteins to function in the right places at the right times. 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. However, only a small percentage of mutations cause genetic disorders, most have no impact on health. For example, some mutations alter a gene's DNA base sequence but don’t change the function of the protein made by the gene. A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... A genetic disorder, or genetic disease is a disease caused by abnormal expression of one or more genes in a person causing a clinical phenotype. ...

If a mutation is present in a germ cell, this can give rise to offspring that carries the mutation in all of its cells. This is the case in hereditary diseases. On the other hand, a mutation can occur in a somatic cell of an organism. Such mutations will be present in all descendants of this cell, and certain mutations can cause the cell to become malignant, and thus cause cancer. A germ cell is a kind of cell that is part of the germline, and is involved in the reproduction of organisms. ... A genetic disorder, or genetic disease is a disease caused, at least in part, by the genes of the person with the disease. ... When normal cells are damaged beyond repair, they are eliminated by apoptosis. ...

Often, gene mutations that could cause a genetic disorder are repaired by the DNA repair system of the cell. 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. DNA damage resulting in multiple broken chromosomes DNA repair is a process constantly operating in cells; it is essential to survival because it protects the genome from damage. ...

A very small percentage of all mutations actually have a positive effect. These mutations lead to new versions of proteins that help an organism and its future generations better adapt to changes in their environment. For example, a beneficial mutation could result in a protein that protects the organism from a new strain of bacteria.

Mutagenesis

Mutagenesis (the creation or formation of a mutation) can be used as a powerful genetic tool. By inducing mutations in specific ways and then observing the phenotype of the organism the function of genes and even individual nucleotides can be determined.

See:
Transposons as a genetic tool for the use of transposable elements for analysis of gene function. Site-directed mutagenesis for the use of site specific mutation for analysis of function. Transposons semi-parasitic DNA sequences which can replicate and spread through the hosts genome. ... (in vitro mutagenesis) Site-directed mutagenesis is a molecular biology technique in which a mutation is created at a defined site in a DNA molecule, usually a circular molecule known as a plasmid. ...

See also

• Homeobox
• Macromutation
• Mutant

A homeobox is a stretch of DNA sequence found in genes involved in the regulation of the development (morphogenesis) of animals, fungi and plants. ... Most biologists believe that adaptation occurs through the accumulation of small mutations. ... A mutant (also known to early geneticists as a monster) is an individual, organism, or new genetic character arising or resulting from an instance of mutation, which is a sudden structural change within the DNA of a gene or chromosome of an organism resulting in the creation of a new...

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.

Online books

• Chapter 7, The Molecular Basis of Mutation in Modern Genetic Analysis by Anthony J. F. Griffiths, William M. Gelbart, Jeffrey H. Miller and Richard C. Lewontin (1999) published by W. H. Freeman and Company ISBN 0-7167-3597-0.
• Chapter 9, Instability of the human genome: mutation and DNA repair in Human Molecular Genetics 2 by Tom Strachan and Andrew P. Read (1999) published by John Wiley & Sons, Inc.
• Genes and Disease from the National Library of Medicine provides descriptions of mutations that cause human diseases. For example, a common mutation associated with Huntington disease is an increased number of copies of repeated CGA triplets in the Huntingtin gene.
• GeneReviews by Roberta A. Pagon, Editor-in-chief is made available by the University of Washington and contains peer-reviewed descriptions of heritable diseases written by experts. For example, BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer describes mutations in BRCA1 and BRCA2 that are associated with predispositions to cancer.

Richard Charles Dick Lewontin (born March 29, 1929) is an American evolutionary biologist, geneticist and social commentator. ... The U.S. National Library of Medicine (NLM), operated by the U.S. federal government, is the worlds largest medical research library. ... Huntingtin is the protein that causes Huntingtons disease. ... The University of Washington, founded in 1861, is a major public research university in the Seattle metropolitan area. ... BRCA 1 (named for breast cancer 1) is a human gene located on the long arm of the 17th chromosome (17q21). ... BRCA2 refers to either a gene (BReast-CAncer susceptibility gene 2, located on human chromosome 13, 13q12-13) or the protein coded for by that gene. ...

External links

• The mutations chapter of the WikiBooks General Biology textbook
• EvoWiki: Mutation
• http://www.gate.net/~rwms/EvoMutations.html Examples of Beneficial Mutations