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| {{dablink|For other senses of this word, see ].}} | |||
| {{evolution3}} | |||
| In ], '''mutations''' are changes to the ] sequence of ] (either ] or ]). Mutations can be caused by copying errors in the genetic material during ] and by exposure to ] or ] radiation, chemical ], or ], or can occur deliberately under cellular control during processes such as ] or ]. In multicellular organisms, mutations can be subdivided into '']s'', which can be passed on to descendants, and '']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 ], and the less favorable (or ''deleterious'') mutations are removed from the gene pool by ], while more favorable (''beneficial'' or ''advantageous'') ones tend to accumulate, resulting in ] change. For example, a butterfly may develop offspring with a new mutation caused say by ultraviolet light from the sun, in most case 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 definitely an advantage and the chances of this butterfly surviving and producing its own offspring are a little better, over time the number of butterflies with this mutation may form a large percentage of the species. ] are defined as mutations whose effects do not influence the ] of either the species or the individuals who make up the species. These can accumulate over time due to ]. The overwhelming majority of mutations have no significant effect, since ] 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=== | |||
| The Hardeep 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: | |||
| ** ''']s''', often caused by chemicals or malfunction of DNA replication, exchange a single ] for another. Most common is the ] that exchanges a ] for a purine (A ↔ G) or a ] for a pyrimidine, (C ↔ T). A transition can be caused by ], base mispairing, or mutagenic base analogs such as ]. Less common is a ], 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 ] (A) being converted into a ] (C). There are also many other examples that can be found. Point mutations that occur within the ] coding region of a gene may be classified into three kinds, depending upon what the erroneous ] codes for: | |||
| *** ]s: which code for the same ]. | |||
| *** ]s: which code for a different amino acid. | |||
| *** ]s: which code for a stop and can truncate the ]. | |||
| ** ''']''' add one or more extra nucleotides into the DNA. They are usually caused by ]s, or errors during replication of repeating elements (e.g. AT repeats). Insertions in the coding region of a gene may alter ] of the ] (]), or cause a shift in the ] (]), both of which can significantly alter the gene product. Insertions can be reverted by excision of the ]. | |||
| ** ''']''' remove one or more nucleotides from the DNA. Like insertions, these mutations can alter the ] of the gene. They are irreversible. | |||
| * Large-scale mutations in ] structure, including: | |||
| ** '''Amplifications''' (or ]s) leading to multiple copies of chromosomal regions, increasing the dosage of the genes located within them. | |||
| ** ''']''' 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 ]s (e.g. ]). These include: | |||
| *** ''']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 ], 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). | |||
| *** ''']s''': reversing the orientation of a chromosomal segment. | |||
| **''']''': loss of one ], either by a deletion or ] 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 (]) it is often called an '''] mutation'''. Phenotypes associated with such mutations are most often ]. Exceptions are when the organism is ], or when the reduced dosage of a normal gene product is not enough for a normal phenotype (this is called ]). | |||
| * '''Gain-of-function mutations''' change the gene product such that it gains a new and abnormal function. These mutations usually have ] phenotypes. Often called a ] mutation. | |||
| * '''Dominant negative mutations''' (also called '''] 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 ] or ] phenotype. In humans, ] is an example of a dominant negative mutation occurring in an ] 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 ]s. | |||
| '''Spontaneous mutations''' on the molecular level include: | |||
| * ] - A base is changed by the repositioning of a hydrogen atom. | |||
| * ] - Loss of a purine base (A or G). | |||
| * ] - 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. | |||
| ], the major mutagen in ], in an adduct to DNA. Produced from .]] | |||
| '''Induced mutations''' on the molecular level can be caused by: | |||
| * Chemicals | |||
| ** Nitrosoguanidine (NTG) | |||
| ** Hydroxyamine NH3OH | |||
| ** ]s (e.g. ]) | |||
| ** Simple chemicals (e.g. ]s) | |||
| ** Alkylating agents (e.g. ]) 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. ] (EMS)) | |||
| ** Polycyclic ] (e.g. ]s found in ] ]) | |||
| ** DNA intercalating agents (e.g. ]) | |||
| ** ] (e.g. ]) | |||
| ** Oxidative damage caused by ](O)] ]s | |||
| * Radiation | |||
| ** ] 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. | |||
| ** ] | |||
| DNA has so-called hotspots, where mutations occur up to 100 times more frequently than the normal ]. A hotspot can be at an unusual base, e.g., ]. | |||
| ]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 (]). | |||
| ==Mutation and disease== | |||
| Changes in DNA caused by mutation can cause errors in ] 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 ]. 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 ], it can give rise to offspring that carries the mutation in all of its cells. This is the case in ]s. On the other hand, a mutation can occur in a ] 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 ]. | |||
| Often, gene mutations that could cause a genetic disorder are repaired by the ] 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. | |||
| 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 ] resistance to ] and delays ] onset in ]. The CCR5 mutaion is more common in those of european descent. One theory for the ] of the relatively high frequency of CCR5-32 in the euopean population is that is conferred resistance to the ] in mid-14th century Europe . | |||
| ==See also== | |||
| * ] | |||
| * ] | |||
| * ] | |||
| * ] | |||
| * ] - An example of how genetics affects colour in budgerigar parakeets. | |||
| ==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, in ''Modern Genetic Analysis'' by Anthony J. F. Griffiths, William M. Gelbart, Jeffrey H. Miller and ] (1999) published by W. H. Freeman and Company ISBN 0-7167-3597-0. | |||
| * Chapter 9, in ''Human Molecular Genetics 2'' by Tom Strachan and Andrew P. Read (1999) published by John Wiley & Sons, Inc. | |||
| * '''' from the ] provides descriptions of mutations that cause human diseases. For example, a common mutation associated with is an increased number of copies of repeated CGA triplets in the ] gene. | |||
| * '''' by Roberta A. Pagon, Editor-in-chief is made available by the ] and contains peer-reviewed descriptions of heritable diseases written by experts. For example, describes mutations in ] and ] that are associated with predispositions to cancer. | |||
| ==External links== | |||
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