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In [[biology]], '''mutations''' are changes to the [[base pair]] sequence of [[genetic material]] (either [[DNA]] or [[RNA]]). Mutations can be caused by copying errors in the genetic material during [[cell division]] and by exposure to [[ultraviolet]] or [[ionizing radiation|ionizing]] radiation, chemical [[mutagens]], or [[virus (biology)|viruses]], or can occur deliberately under cellular control during processes such as [[meiosis]] or [[hypermutation]]. In multicellular organisms, mutations can be subdivided into ''[[germline mutation]]s'', which can be passed on to descendants, and ''[[somatic mutation]]s''. The somatic mutations cannot be transmitted to descendants in animals. Plants sometimes can transmit somatic mutations to their descendants asexually or sexually (in case when flower buds develop in somatically mutated part of plant).
Mutations create variation in the [[gene pool]], and the less favorable (or ''deleterious'') mutations are removed from the gene pool by [[natural selection]], while more favorable (''beneficial'' or ''advantageous'') ones tend to accumulate, resulting in [[evolution]]ary change. For example, a butterfly may develop offspring with a new mutation caused say by ultraviolet light from the sun. In most cases, this mutation is not good, since obviously there was no 'purpose' for such change at the molecular level. However, sometimes a mutation may change, say, the butterfly's color, making it harder for predators to see it; this is an advantage and the chances of this butterfly surviving and producing its own offspring are a little better, and over time the number of butterflies with this mutation may form a large percentage of the species. [[Neutral theory of molecular evolution|Neutral mutations]] are defined as mutations whose effects do not influence the [[Fitness (biology)|fitness]] of either the species or the individuals who make up the species. These can accumulate over time due to [[genetic drift]]. The overwhelming majority of mutations have no significant effect, since [[DNA repair]] is able to mend most changes before they become permanent mutations, and many organisms have mechanisms for eliminating otherwise permanently mutated somatic cells.
==Classification==
===By effect on structure===
[[Image:Types-of-mutation.png|thumb|Illustrations of five types of chromosomal mutations.]]
The 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, such as affecting a small gene is one or a few nucleotides, including:
** '''[[Point mutation]]s''', often caused by chemicals or malfunction of DNA replication, exchange a single [[nucleotide]] for another. Most common is the [[transition (genetics)|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 [[BrdU|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]] (A) being converted into a [[cytosine]] (C). There are also many other examples that can be found. Point mutations that occur within the [[protein]] coding region of a gene may be classified into three kinds, depending upon what the erroneous [[codon]] codes for:
*** [[Silent mutation]]s: which code for the same [[amino acid]].
*** [[Missense mutation]]s: which code for a different amino acid.
*** [[Nonsense mutation]]s: which code for a stop and can truncate the [[protein]].
** '''[[insertion (genetics)|Insertions]]''' add one or more extra nucleotides into the DNA. They are usually caused by [[transposable element]]s, or errors during replication of repeating elements (e.g. AT repeats). Insertions in the coding region of a gene may alter [[splicing (genetics)|splicing]] of the [[mRNA]] ([[splice site mutation]]), 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]].
** '''[[Genetic deletion|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 [[chromosome|chromosomal]] structure, including:
** '''Amplifications''' (or [[gene duplication]]s) leading to multiple copies of all chromosomal regions, increasing the dosage of the genes located within them.
** '''[[Genetic deletion|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 gene]]s (e.g. [[bcr-abl]]). These include:
*** '''[[Chromosomal translocation]]s''': interchange of genetic parts from nonhomologous chromosomes.
*** '''Interstitial deletions''': an intra-chromosomal deletion that removes a segment of DNA from a single chromosome, thereby apposing previously distant genes. For example, cells isolated from a human [[astrocytoma]], a type of brain tumor, were found to have a chromosomal deletion removing sequences between the "fused in glioblastoma" (fig) gene and the receptor tyrosine kinase "ros", producing a fusion protein (FIG-ROS). The abnormal FIG-ROS fusion protein has constitutively active kinase activity that causes oncogenic transformation (a transformation from normal cells to cancer cells).
*** '''[[Chromosomal inversion]]s''': reversing the orientation of a chromosomal segment.
**'''[[Loss of heterozygosity]]''': loss of one [[allele]], either by a deletion or [[recombination]] event, in an organism that previously had two different alleles.
===By effect on function===
* '''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 '''[[Muller's morphs|amorphic]] mutation'''. Phenotypes associated with such mutations are most often [[recessive]]. Exceptions are when the organism is [[haploid]], or when the reduced dosage of a normal gene product is not enough for a 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 gene|dominant]] phenotypes. Often called a [[Muller's morphs|neomorphic]] mutation.
* '''Dominant negative mutations''' (also called '''[[Muller's morphs|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 gene|dominant]] or [[incomplete dominance|semi-dominant]] phenotype. In humans, [[Marfan syndrome]] is an example of a dominant negative mutation occurring in an [[autosomal dominant]] disease. In this condition, the defective glycoprotein product of the fibrillin gene (FBN1) antagonizes the product of the normal allele.
*'''Lethal mutations''' are mutations that lead to a phenotype incapable of effective reproduction.
===By aspect of phenotype affected===
* '''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.
===Special classes===
*'''Conditional mutation''' is a mutation that has wild-type (or less severe) phenotype under certain "permissive" environmental conditions and a mutant phenotype under certain "restrictive" conditions. For example, a temperature-sensitive mutation can cause cell death at high temperature (restrictive condition), but might have no deletirious consequences at a lower temperature (permissive condition).
===Causes of mutation===
Two classes of mutations are spontaneous mutations (molecular decay) and induced mutations caused by [[mutagen]]s.
'''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 deamination of 5-methycytosine (irreparable), 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.
[[Image:Pyrene adduct.jpg|thumb|right|250px|[[Benzopyrene]], the major mutagen in [[Tobacco smoking|tobacco smoke]], in an adduct to DNA. Produced from [http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1JDG PDB 1JDG].]]
'''Induced mutations''' on the molecular level can be caused by:
* Chemicals
** Nitrosoguanidine (NTG)
** Hydroxyamine NH3OH
** [[Base analog]]s (e.g. [[BrdU]])
** Simple chemicals (e.g. [[acid]]s)
** Alkylating agents (e.g. [[ENU|''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. [[ethyl methanesulfonate]] (EMS))
** Polycyclic [[hydrocarbons]] (e.g. [[benzopyrene]]s found in [[internal combustion engine]] [[exhaust]])
** DNA intercalating agents (e.g. [[ethidium bromide]])
** [[DNA crosslinker]] (e.g. [[platinum]])
** Oxidative damage caused by [[oxygen]](O)] [[Radical (chemistry)|radical]]s
* Radiation
** [[Ultraviolet]] radiation (nonionizing radiation) - excites electrons to a higher energy level. DNA absorbs one form, ultraviolet light. Two nucleotide bases in DNA - cytosine and thymine-are most vulnerable to excitation that can change base-pairing properties. UV light can induce adjacent thymine bases in a DNA strand to pair with each other, as a bulky dimer.
** [[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 rate]]s 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 genotype|mutator strains]]).
==Harmful mutations==
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.
If a mutation is present in a [[germ cell]], it can give rise to offspring that carries the mutation in all of its cells. This is the case in [[hereditary disease]]s. 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]].
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.
==Beneficial mutations==
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 specfic 32 base pair deletion in human CCR5 (CCR5-32) confers [[HIV]] resistance to [[Zygosity|homozygotes]] and delays [[AIDS]] onset in [[Zygosity|heterozygotes]].<ref>[http://www.cdc.gov/genomics/hugenet/factsheets/FS_CCR5.htm]</ref> The CCR5 mutation is more common in those of European descent. One theory for the [[etiology]] of the relatively high frequency of CCR5-32 in the euopean population is that is conferred resistance to the [[bubonic plague]] in mid-14th century Europe.<ref>[http://www.pbs.org/wnet/secrets/case_plague/clues.html]</ref>
==See also==
* [[Macromutation]]
* [[Mutant]]
* [[Antioxidant]]
* [[Muller's morphs]]
* [[Homeobox]]
* [[Budgerigar colour genetics]] - An example of how genetics affects colour in budgerigar parakeets.
==References==
<references/>
* Leroi A. 2003. ''Mutants: On the form, varieties & errors of the human body''. 1:16-17. Harper Collins 2003
* 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.
* Taggart R. Starr C. ''Biology The Unity and Diversity of Life: Mutated Genes and Their Protein Products''. 14.4:227. Thompson Brooks/Cole 2006.
===Online books===
* Chapter 7, [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=mutation+AND+mga%5Bbook%5D+AND+110363%5Buid%5D&rid=mga.section.996 The Molecular Basis of Mutation] in ''Modern Genetic Analysis'' by Anthony J. F. Griffiths, William M. Gelbart, Jeffrey H. Miller and [[Richard Lewontin|Richard C. Lewontin]] (1999) published by W. H. Freeman and Company ISBN 0-7167-3597-0.
* Chapter 9, [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hmg.section.1050 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.
* ''[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.preface.91 Genes and Disease]'' from the [[National Library of Medicine]] provides descriptions of mutations that cause human diseases. For example, a common mutation associated with [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=mutation+AND+gnd%5Bbook%5D+AND+138070%5Buid%5D&rid=gnd.section.207 Huntington disease] is an increased number of copies of repeated CGA triplets in the [[Huntingtin]] gene.
* ''[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=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, [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gene.chapter.brca1 BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer] describes mutations in [[BRCA1]] and [[BRCA2]] that are associated with predispositions to cancer.
==External links==
* [[Wikibooks:Mutation (General Biology)|The mutations chapter of the WikiBooks General Biology textbook]]
* [http://www.gate.net/~rwms/EvoMutations.html Examples of Beneficial Mutations]
* [http://www.q-pharm.com/home/contents/drug_d/order_form/online_services/mutagenesis Software for Mutated Proteins' Activity Prediction]
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no edit summary
In [[biology]], '''mutations''' are changes to the [[base pair]] sequence of [[genetic material]] (either [[DNA]] or [[RNA]]). Mutations can be caused by copying errors in the genetic material during [[cell division]] and by exposure to [[ultraviolet]] or [[ionizing radiation|ionizing]] radiation, chemical [[mutagens]], or [[virus (biology)|viruses]], or can occur deliberately under cellular control during processes such as [[meiosis]] or [[hypermutation]]. In multicellular organisms, mutations can be subdivided into ''[[germline mutation]]s'', which can be passed on to descendants, and ''[[somatic mutation]]s''. The somatic mutations cannot be transmitted to descendants in animals. Plants sometimes can transmit somatic mutations to their descendants asexually or sexually (in case when flower buds develop in somatically mutated part of plant).
Mutations create variation in the [[gene pool]], and the less favorable (or ''deleterious'') mutations are removed from the gene pool by [[natural selection]], while more favorable (''beneficial'' or ''advantageous'') ones tend to accumulate, resulting in [[evolution]]ary change. For example, a butterfly may develop offspring with a new mutation caused say by ultraviolet light from the sun. In most cases, this mutation is not good, since obviously there was no 'purpose' for such change at the molecular level. However, sometimes a mutation may change, say, the butterfly's color, making it harder for predators to see it; this is an advantage and the chances of this butterfly surviving and producing its own offspring are a little better, and over time the number of butterflies with this mutation may form a large percentage of the species. [[Neutral theory of molecular evolution|Neutral mutations]] are defined as mutations whose effects do not influence the [[Fitness (biology)|fitness]] of either the species or the individuals who make up the species. These can accumulate over time due to [[genetic drift]]. The overwhelming majority of mutations have no significant effect, since [[DNA repair]] is able to mend most changes before they become permanent mutations, and many organisms have mechanisms for eliminating otherwise permanently mutated somatic cells.
==Classification==
===By effect on structure===
[[Image:Types-of-mutation.png|thumb|Illustrations of five types of chromosomal mutations.]]
The 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, such as affecting a small gene is one or a few nucleotides, including:
** '''[[Point mutation]]s''', often caused by chemicals or malfunction of DNA replication, exchange a single [[nucleotide]] for another. Most common is the [[transition (genetics)|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 [[BrdU|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]] (A) being converted into a [[cytosine]] (C). There are also many other examples that can be found. Point mutations that occur within the [[protein]] coding region of a gene may be classified into three kinds, depending upon what the erroneous [[codon]] codes for:
*** [[Silent mutation]]s: which code for the same [[amino acid]].
*** [[Missense mutation]]s: which code for a different amino acid.
*** [[Nonsense mutation]]s: which code for a stop and can truncate the [[protein]].
** '''[[insertion (genetics)|Insertions]]''' add one or more extra nucleotides into the DNA. They are usually caused by [[transposable element]]s, or errors during replication of repeating elements (e.g. AT repeats). Insertions in the coding region of a gene may alter [[splicing (genetics)|splicing]] of the [[mRNA]] ([[splice site mutation]]), 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]].
** '''[[Genetic deletion|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 [[chromosome|chromosomal]] structure, including:
** '''Amplifications''' (or [[gene duplication]]s) leading to multiple copies of all chromosomal regions, increasing the dosage of the genes located within them.
** '''[[Genetic deletion|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 gene]]s (e.g. [[bcr-abl]]). These include:
*** '''[[Chromosomal translocation]]s''': interchange of genetic parts from nonhomologous chromosomes.
*** '''Interstitial deletions''': an intra-chromosomal deletion that removes a segment of DNA from a single chromosome, thereby apposing previously distant genes. For example, cells isolated from a human [[astrocytoma]], a type of brain tumor, were found to have a chromosomal deletion removing sequences between the "fused in glioblastoma" (fig) gene and the receptor tyrosine kinase "ros", producing a fusion protein (FIG-ROS). The abnormal FIG-ROS fusion protein has constitutively active kinase activity that causes oncogenic transformation (a transformation from normal cells to cancer cells).
*** '''[[Chromosomal inversion]]s''': reversing the orientation of a chromosomal segment.
**'''[[Loss of heterozygosity]]''': loss of one [[allele]], either by a deletion or [[recombination]] event, in an organism that previously had two different alleles.
===By effect on function===
* '''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 '''[[Muller's morphs|amorphic]] mutation'''. Phenotypes associated with such mutations are most often [[recessive]]. Exceptions are when the organism is [[haploid]], or when the reduced dosage of a normal gene product is not enough for a 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 gene|dominant]] phenotypes. Often called a [[Muller's morphs|neomorphic]] mutation.
* '''Dominant negative mutations''' (also called '''[[Muller's morphs|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 gene|dominant]] or [[incomplete dominance|semi-dominant]] phenotype. In humans, [[Marfan syndrome]] is an example of a dominant negative mutation occurring in an [[autosomal dominant]] disease. In this condition, the defective glycoprotein product of the fibrillin gene (FBN1) antagonizes the product of the normal allele.
*'''Lethal mutations''' are mutations that lead to a phenotype incapable of effective reproduction.
===By aspect of phenotype affected===
* '''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.
===Special classes===
*'''Conditional mutation''' is a mutation that has wild-type (or less severe) phenotype under certain "permissive" environmental conditions and a mutant phenotype under certain "restrictive" conditions. For example, a temperature-sensitive mutation can cause cell death at high temperature (restrictive condition), but might have no deletirious consequences at a lower temperature (permissive condition).
===Causes of mutation===
Two classes of mutations are spontaneous mutations (molecular decay) and induced mutations caused by [[mutagen]]s.
'''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 deamination of 5-methycytosine (irreparable), 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.
[[Image:Pyrene adduct.jpg|thumb|right|250px|[[Benzopyrene]], the major mutagen in [[Tobacco smoking|tobacco smoke]], in an adduct to DNA. Produced from [http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1JDG PDB 1JDG].]]
'''Induced mutations''' on the molecular level can be caused by:
* Chemicals
** Nitrosoguanidine (NTG)
** Hydroxyamine NH3OH
** [[Base analog]]s (e.g. [[BrdU]])
** Simple chemicals (e.g. [[acid]]s)
** Alkylating agents (e.g. [[ENU|''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. [[ethyl methanesulfonate]] (EMS))
** Polycyclic [[hydrocarbons]] (e.g. [[benzopyrene]]s found in [[internal combustion engine]] [[exhaust]])
** DNA intercalating agents (e.g. [[ethidium bromide]])
** [[DNA crosslinker]] (e.g. [[platinum]])
** Oxidative damage caused by [[oxygen]](O)] [[Radical (chemistry)|radical]]s
* Radiation
** [[Ultraviolet]] radiation (nonionizing radiation) - excites electrons to a higher energy level. DNA absorbs one form, ultraviolet light. Two nucleotide bases in DNA - cytosine and thymine-are most vulnerable to excitation that can change base-pairing properties. UV light can induce adjacent thymine bases in a DNA strand to pair with each other, as a bulky dimer.
** [[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 rate]]s 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 genotype|mutator strains]]).
==Harmful mutations==
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.
If a mutation is present in a [[germ cell]], it can give rise to offspring that carries the mutation in all of its cells. This is the case in [[hereditary disease]]s. 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]].
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.
==Beneficial mutations==
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 specfic 32 base pair deletion in human CCR5 (CCR5-32) confers [[HIV]] resistance to [[Zygosity|homozygotes]] and delays [[AIDS]] onset in [[Zygosity|heterozygotes]].<ref>[http://www.cdc.gov/genomics/hugenet/factsheets/FS_CCR5.htm]</ref> The CCR5 mutation is more common in those of European descent. One theory for the [[etiology]] of the relatively high frequency of CCR5-32 in the euopean population is that is conferred resistance to the [[bubonic plague]] in mid-14th century Europe.<ref>[http://www.pbs.org/wnet/secrets/case_plague/clues.html]</ref>
==See also==
* [[Macromutation]]
* [[Mutant]]
* [[Antioxidant]]
* [[Muller's morphs]]
* [[Homeobox]]
* [[Budgerigar colour genetics]] - An example of how genetics affects colour in budgerigar parakeets.
==References==
<references/>
* Leroi A. 2003. ''Mutants: On the form, varieties & errors of the human body''. 1:16-17. Harper Collins 2003
* 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.
* Taggart R. Starr C. ''Biology The Unity and Diversity of Life: Mutated Genes and Their Protein Products''. 14.4:227. Thompson Brooks/Cole 2006.
===Online books===
* Chapter 7, [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=mutation+AND+mga%5Bbook%5D+AND+110363%5Buid%5D&rid=mga.section.996 The Molecular Basis of Mutation] in ''Modern Genetic Analysis'' by Anthony J. F. Griffiths, William M. Gelbart, Jeffrey H. Miller and [[Richard Lewontin|Richard C. Lewontin]] (1999) published by W. H. Freeman and Company ISBN 0-7167-3597-0.
* Chapter 9, [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hmg.section.1050 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.
* ''[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.preface.91 Genes and Disease]'' from the [[National Library of Medicine]] provides descriptions of mutations that cause human diseases. For example, a common mutation associated with [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=mutation+AND+gnd%5Bbook%5D+AND+138070%5Buid%5D&rid=gnd.section.207 Huntington disease] is an increased number of copies of repeated CGA triplets in the [[Huntingtin]] gene.
* ''[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=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, [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gene.chapter.brca1 BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer] describes mutations in [[BRCA1]] and [[BRCA2]] that are associated with predispositions to cancer.
==External links==
* [[Wikibooks:Mutation (General Biology)|The mutations chapter of the WikiBooks General Biology textbook]]
* [http://www.gate.net/~rwms/EvoMutations.html Examples of Beneficial Mutations]
* [http://www.q-pharm.com/home/contents/drug_d/order_form/online_services/mutagenesis Software for Mutated Proteins' Activity Prediction]
{{evolution}}
[[Category:Evolutionary biology]]
[[Category:Genetics]]
[[Category:Mutation|*]]
[[ar:طفرة]]
[[bg:Мутация]]
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[[gl:Mutación]]
[[ko:돌연변이]]
[[id:Mutasi]]
[[it:Mutazione genetica]]
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[[th:การกลายพันธุ์]]
[[vi:Đột biến sinh học]]
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