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 Mutations & Mutagenesis

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اوسمه : Mutations & Mutagenesis Modera10

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Mutations & Mutagenesis Empty
مُساهمةموضوع: Mutations & Mutagenesis   Mutations & Mutagenesis Emptyالثلاثاء فبراير 08, 2011 7:00 pm

Mutations - or changes to the nucleotide sequence of DNA - can arise in a number of ways. Mistakes can be made during DNA replication that result in the incorporation of an incorrect base. The chemical nature of any given base can be altered either by environmental or chemical means. Once altered, these changes may then be propagated by further DNA replication. Finally, large scale changes can sometimes occur in the form of DNA insertions and/or deletions.

Types of Mutations
We can consider the following broad categories of mutations:
SINGLE BASE PAIR CHANGES
Single mutations (or point mutations) involve a change in the identity of a single base or base-pair.
There are two types of mutation that change the identity of a base (base-pair)
TRANSITIONS
Transitions do not alter the chemical nature of the base. Thus, a purine base is replaced by another purine; a pyrimidine is replaced by a pyrimidine.
The only transitions are:
A -> G or G -> A
C -> T or T -> C

TRANSVERSIONS
Transversions change the the chemical nature of the base. Thus, a purine base is replaced by a pyrimidine; a pyrimidine is replaced by a purine.
The transversions are:
A -> C or A -> T
C -> A or C -> G
G -> C or G -> T
T -> A or T -> G

These types of mutation can arise as a result of errors during DNA replication caused by tautomerization or by chemical reactions such as oxidation. Tautomerization generates transitions as does oxidative deamination. Oxidation of guanine generates transversions.
Base pair changes are not necessarily deleterious -- a change in genotype need not necessarily cause any change in phenotype. It depends on whether the change occurs within a coding region or within some other important regulatory sequence (e.g. an operator or promoter).
SILENT mutations occur when a base pair change in a coding region does not affect the amino acid that is encoded. For example, the change UGC -> UGU is silent because both are codons for cysteine. Another way in which silent mutations might occur is when the change occurs in a non-coding or non-regulatory region.
MISSENSE mutations occur when the base pair change in a coding region results in a change the amino acid that is encoded. How severe the mutation may depends on the nature of the change. For example, the change GAA -> GAU will result in a change from glutamic acid to aspartic acid. One would not expect this change to have a very large effect. However, the change GAA -> AAA would be expected to be significant since it replaces a glutamic acid with a lysine.
NONSENSE mutations occur when the base pair change in a coding region results in the creation of a stop codon. Proteins will be truncated as a result of this type of mutation. An example is the change UGC -> UGA.

INSERTION/DELETION MUTATIONS
These types of changes can be small in scope or very large in scope.
FRAMESHIFT MUTATIONS
By definition, these mutations only occur within reading frames and can involve the insertion or deletion of one or a few base pairs. They can occur as a result of "slippage" during DNA replication. They can also arise as a result of intercalating mutagens such as ethidium bromide and acridine orange.
INSERTIONS & DELETIONS
Deletions can be very large. The only real limitation on the amount of DNA that can be deleted as a result of mutation is that no essential genes can be deleted. Deletions can arise as a result of recombination between repeated sequences.
Insertion mutations are usually due to a large piece of DNA, such as an Insertion Sequence or a Transposon, moving into a specific site. This type of mutation will usually inactivate a gene.

Spontaneous Mutagenesis
Spontaneous mutations can arise as a result of chemical changes to individual bases in DNA. These types of changes are sometimes associated with DNA replication. Some examples are:
TAUTOMERIZATION of either the template base or the base in the nucleotide being added may result in incorrect pairing in the active site of DNA polymerase and, in turn, result in the incorporation of an incorrect base. These types of mistakes are usuallt detected by the proof-reading exonuclease. However, when they are not, they must be repaired by the MISMATCH REPAIR system.
[S31-39 S31-40]
DEAMINATION of cytosine can occur spontaneously or as a result of treatment with nitrous acid. This reaction results in the deamination of cytosine to uracil which can then base pair with adenine. Since uracil is a "normal" base - although it only normally occurs in RNA - this is potentially a very serious problem. The cell, however, has an enzyme to remove it from DNA: uracil-N-glycosylase.
[24-25] [S31-42]
NUCLEOTIDE BASE ANALOGUES, if they are present, can be incorporated into DNA during replication and result in erroneous pairing. One examples is 5-bromo-uracil. This base tautomerizes more readily than thymine. As a result, it will pair with guanine more frequently. and the result is a TA -> CG transition.
[24-24] [S31-41]
PYRIMIDINE DIMERS form between two adjacent pyrimidine bases when DNA is exposed to UV light. The most common dimer occurs when the conjugated ring systems of adjacent thymine bases in a polynucleotide chain absorb UV light and form a cyclobutane ring which links carbons 5 and 6 of each pyrimidine ring to one another.
[24-23]
ALKYLATION of DNA can result in mutations in several ways. The addition of bulky alkyl groups by chemicals such as ethyl methane sulfonate (nitrogen mustard gas) or ethylnitrosourea will distort the DNA double helix. The modified nucleotides can be excised but the gaps are often repaired incorrectly.
Methylation of DNA can be a mixed blessing. It is an important reaction for regulating gene expression in eukaryotes and for marking the host cell DNA in bacteria. However, some methylated bases such as 5-methyl cytosine, are more susceptible to oxidative deamination. For this reason, the methylation system is often accompanied by a special repair system.

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مُساهمةموضوع: رد: Mutations & Mutagenesis   Mutations & Mutagenesis Emptyالإثنين فبراير 14, 2011 5:24 pm

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اوسمه : Mutations & Mutagenesis Modera10

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عدد الرسائل : 2879
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Mutations & Mutagenesis Empty
مُساهمةموضوع: رد: Mutations & Mutagenesis   Mutations & Mutagenesis Emptyالثلاثاء فبراير 15, 2011 10:13 am

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مُساهمةموضوع: رد: Mutations & Mutagenesis   Mutations & Mutagenesis Emptyالثلاثاء فبراير 15, 2011 5:41 pm

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