A Detailed Overview of DNA Mutations
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A Detailed Overview of DNA Mutations

There are two types of mutations, spontaneous and induced. The first type, as is specified by its name, is a naturally occurring DNA mutation that can arise in all cells. The second set of mutations arises from the action of certain agents known as mutagens. These mutagens increase the rate at which mutations occur. However, both spontaneous and induced mutations are random, which is significant because it allows for genetic diversity within a species over time.

There are two types of mutations, spontaneous and induced. The first type, as is specified by its name, is a naturally occurring DNA mutation that can arise in all cells.  The second set of mutations arises from the action of certain agents known as mutagens.  These mutagens increase the rate at which mutations occur.  However, both spontaneous and induced mutations are random, which is significant because it allows for genetic diversity within a species over time. 

            Both spontaneous and induced mutations can cause a mutation in one of the following ways: synonymous, missense conservative, missense non-conservative, nonsense, or as an insertion deletion (indel).  A synonymous mutation is where a change in a base causes no change in the amino acid and therefore no change in protein function.  A missense conservative mutation is one where a base change does cause a change in the amino acid but the overall protein function remains the same or similar.  This is due to a chemically similar amino acid replacing the original.  A missense non-conservative mutation is where a change in the base causes a change in the amino acid which overall changes the function of the protein being transcribed.  A nonsense mutation simply puts a stop codon where the mutation occurred.  Indels are the more serious mutations because they cause frame-shifts in the DNA which causes the entire amino acid sequence after the mutation to be out of sync seriously changing the amino acid sequence and the protein the DNA was to code for.  The first four mutations are what is known as transition/transversion mutations.  A transition mutation is where a purine is replaced by another purine (A or G) or a pyrimidine is replaced by another pyrimidine (C or T).  Transversions are when a purine is replaced by a pyrimidine or vice versa.

            Naturally occurring damage to DNA can be a leading cause for spontaneous mutations.  One such example is depurinitation, the loss of a purine base due to a break in the glycosidic bond between the base and the sugar-phosphate backbone.  According to Introduction to Genetic Analysis by A. Griffiths, mutations such as these cause the spontaneous loss of about 10,000 purines from its DNA in a 20-hour cell cycle period.  Damage such as this can be repaired by the base excision repair pathway which puts and incorrect base in place of the purine that would have been there.  As a result, after replication, only a transition or transition or transversion mutation has occurred and not an indel mutation.  Another type of spontaneous mutation caused by damaged DNA is deanimation, the transversion of a cytosine to a uracil.  After replication, uracil pairs with adenine thereby converting a C G pair into an A T pair.  Thirdly, oxidative damage is yet another form of a spontaneous mutation.  This type of mutation is caused by the production of superoxide radicals (O2-), hydrogen peroxide (H2O2), and hydroxyl radicals (OH) in normal aerobic respiration.

            Again induced mutations are caused by mutagens.  The production of mutagens comes about through exposure, known as mutagenesis.  There are three mechanisms of mutagenesis: replacing a base in the DNA, altering a base so that it specifically mis-pairs with another base, or damaging a base so that it can no longer pair with other bases under normal conditions.  Base analogs are a form of the second mechanism.  Analogs of adenine can pair with thymine and mis-pair with cytosine because the adenine is protonated at the 1 carbon site.  Alkylating agents such as ethylmethanesulfate and nitrosoguanidine are another form of mis-pairings where thymine mis-pairs with guanine or vice versa.  5-bromouracil is an abnormal base, which under normal circumstances pairs with adenine, but under abnormal circumstances binds to guanine.  This causes a normally occurring A T pair to transition to a C G pair.  A type of base damage that can cause a mutation is common when the DNA is exposed to UV light.  This causes a cyclobutane pyrimidine photodimer, where two adjacent pyrimiadines bind together and do not recognize their complimentary base pair.  To repair this an enzyme called CPD photolyase unlinks the two pyminadines using light.

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