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, chemical mutagens, or viruses, or can occur deliberately under cellular control during processes such as meiosis or hypermutation. In multicellular organisms, mutations can be subdivided into germline mutations, which can be passed on to descendants, and somatic mutations. 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 evolutionary 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 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 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.
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 (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 mutations: which code for the same amino acid.
Missense mutations: which code for a different amino acid.
Nonsense mutations: which code for a stop and 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 of a gene may alter 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.
Deletions remove one or more nucleotides from the DNA. Like insertions, these mutations can alter the reading frame of the gene. They are irreversible.
Causes of mutation
Two classes of mutations are spontaneous mutations (molecular decay) and induced mutations caused by mutagens.
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.
Benzopyrene, the major mutagen in tobacco smoke, in an adduct to DNA. Produced from PDB 1JDG.
Induced mutations on the molecular level can be caused by:
Chemicals
Nitrosoguanidine (NTG)
Hydroxyamine NH3OH
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. ethyl methanesulfonate (EMS))
Polycyclic hydrocarbons (e.g. benzopyrenes found in internal combustion engine exhaust)
DNA intercalating agents (e.g. ethidium bromide)
DNA crosslinker (e.g. platinum)
Oxidative damage caused by oxygen(O)] radicals
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 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).
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 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.
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 specific 32 base pair deletion in human CCR5 (CCR5-32) confers HIV resistance to homozygotes and delays AIDS onset in heterozygotes.[1] 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 European population is that it conferred resistance to the bubonic plague in mid-14th century Europe.
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 evolutionary 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 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 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.
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 (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 mutations: which code for the same amino acid.
Missense mutations: which code for a different amino acid.
Nonsense mutations: which code for a stop and 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 of a gene may alter 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.
Deletions remove one or more nucleotides from the DNA. Like insertions, these mutations can alter the reading frame of the gene. They are irreversible.
Causes of mutation
Two classes of mutations are spontaneous mutations (molecular decay) and induced mutations caused by mutagens.
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.
Benzopyrene, the major mutagen in tobacco smoke, in an adduct to DNA. Produced from PDB 1JDG.
Induced mutations on the molecular level can be caused by:
Chemicals
Nitrosoguanidine (NTG)
Hydroxyamine NH3OH
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. ethyl methanesulfonate (EMS))
Polycyclic hydrocarbons (e.g. benzopyrenes found in internal combustion engine exhaust)
DNA intercalating agents (e.g. ethidium bromide)
DNA crosslinker (e.g. platinum)
Oxidative damage caused by oxygen(O)] radicals
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 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).
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 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.
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 specific 32 base pair deletion in human CCR5 (CCR5-32) confers HIV resistance to homozygotes and delays AIDS onset in heterozygotes.[1] 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 European population is that it conferred resistance to the bubonic plague in mid-14th century Europe.
Source :wilkepedia
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