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A mutation is a change in the genetic material of a cell that can be passed on from the cell to its daughter cells during the process of cell division. Mutations are important for several reasons. First mutations are the source of new variation important for evolution. Indeed today we biologists consdier mutations to one of the ways that evolution happens. Mutations are also important since they can lead to various human medical conditions including various types of cancer. Mutations can happen on a number of different scales. Some mutations involve only a single base pair in a DNA molecule. These mutations are called point mutations. Other mutations involve rearrangements in big regions of chromosomes. These are called chromosomal mutations. Still other mutations involve changes in chromosomal number.
Somatic vs germ cell mutations
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In multicellualr organisms such as plants or animals mutations may occur in the somatic cells of the organism. Somatic cells are the cells involved in growth and repair and maintenence of the organism. A mutation in these cells may lead to cancer and certains of chromosomal mutations may be involved in aging. Other mutations happen in the germ cells and these mutations may appear in the gametes and then in the offsrping produced by sexual reproduction. These sorts of muutations are called germ cell mutations.
Causes of mutations
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Mutations are often classifies as spontaneous and induced.
Spontaneous mutations are mutations which arise because or errors in the DNA duplication process. As part of this process there is a proof reading mechanism involving one of the DNA polymerases. But this process is not one hundred percent perfect, leading to a low level of mutations per generation. For humans this mutation rate is about 1 x 10-6 mutations per gene locus per generation. This means that it is likely that most of us are carrying at least one new mutation not found in our parents.
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Induced mutations are mutations brought about by exposure to chemicals or various forms of radiation.
Mutagens
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Chemicals which can cause mutations are called mutagens. Mutagens can act on the genetic material in a number of different ways. For example certain carcinogens mimic the shape of the nitrogen bases in DNA and confuse the duplication process. Other mutagens modify the structure of the DNA bases themselves and thus lead to errors in base pairing. Still other mutagens called intercalating agents insert themselves in between bases in the DNA molecule and again confuse the duplication process.
Radiation
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The term radiation refers to high energy subatomoic particles or light energy, more precisely called electromagnetic radiation. What we call visable light is a form of radiation as are 'x-rays' and infrared radiation and microwaves. Radiation is classified as to whether or not it has sufficient energy to break chemical bonds and create ions. Such radiation is called ionizng radiation. X rays are a good example of ionizing radiation. Ionizing radiation can seriously damage DNA molecules and whole chromosomes. Non ionizing radiation cannot typically lead to the formation of ions and is less liekly to induce mutations. However there are some exceptions. Utraviolet (UV) radiation is typically considered to be non ionizing radiation but it is absorbed by DNA and especially affects thymine. Two thymine side by side can join together to forma a so called dimer when exposed to UV resulting in confusion of the duplication process.
From a public health perspective the goal in public health is to minimize additional mutations induced by mutagens and radiation added to the environment by human activity. This is important because many agentgs that induce mutations also cause cancer. For example, the tars in cigarettes are both mutagens and carcinogens(cancer causing chemicals). The same is true for radiation such as UV and radiation produced by naturally occuring unstable isotopes and elements such as radon.
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A point mutation is a mutation involving a change in a single base pair in a DNA molecule. The major types of point mutations are shown below. The basic classification of point mutations is in terms of substitutions and frameshift mutations.
Substitution mutations vs frameshift mutations.
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In substitution mutations a nucleotide with a different nitrogen base replaces a nucleotide in the DNA. In frame shift mutations, a nucleotide is either deleted from or inserted into the DNA.
The figure shows an original DNA tempolate strand( the strand that is going to be transcribed into RNA during transcription), the mRNA that results from this strand and the resulting sequence of amino acids in th polypeptide(here called a peptide since it is only as short sequence of amino acids -met-thr-his-asp-gly resulting from translation of the mRNA. A type of substution called a missense mutation and a type of frameshift mutation involving a deletion of the fouth nucleotide in the original DNA are shown. For each type of mutation the resulting changes in the peptide are shown in yellow.
Notice that substitution mutations can have a relatively minor affect on the sequence of amino acids because only one codon in the mRNA is altered.
The effects of frameshift mutations:
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In frame shift mutations, since a base is either added or removed from a codon, the effect is to shift the codons as read during translation by one position which radically alters the meaning of the mRNA in terms of how it is translated.. Notice in our example the frame shift mutation changes all the amino acids after the first one because codons are in groups of three non overlapping RNA bases.
To illistrate the concept suppose our messenger RNA resulting from the original DNA can be thought of as the following string of letters decoded by reading each group of three non overlapping letters:
THEBIGCATATETHERAT = THE BIG CAT ATE THE RAT
If the third letter(E) in our string is deleted we have:
THBIGCATATETHERAT = THB IGC ATA TET HER AT
which makes no sense when decoded.
Types of substitution mutations
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The following tables compare some of the major types of substitution mutations by looking at their effect on a polypeptide chain. Substitution mutations may vary in effect on the polypeptide resulting from translation. Sometimes as in a silent mutation the mutation does not alter the polypeptide at all. At the other extreme, nonsense mutations may lead to a radically altered polypeptide.
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This table shows the original DNA
template in the first row, then the mRNA divided up into codons followed
by the polypeptide obtained by translating the mRNA |
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Missense mutation
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Missense mutations Previous Page, Next Page , Top of Page This table shows a type of substitution called a missense mutation because a change in a single base in the DNA template results in a change in a single amino acid in the final polypeptide. The changes are shaded. In this missense mutation the original glycine is replaced by arginine, a basic amino acid. This is not either a neutral or a silent missense mutation since an amino acid is replaced with one chemically quite distinct. This sort of missense mutation is likely to cause problems with the structure of the mutant polypeptide. |
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Neutral mutation
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Neutral Mutations Previous Page, Next Page , Top of Page Neutral mutations are a type of missense mutation in which the new amino acid is chmically similar to the one it is replacing. The resulting polypeptide will not be much different from the original polypeptide, in terms of how well it functions, hence the term neutral mutations. When scientists began to examine protein variation they were suprised at how common these neutral mutations can be. Neutral mutations may build up to a high frequency in a population and may represent a hidden sourse of variation important ot a popuilation when the environment changes. In this missense mutation glycine is nonpolar as is alanine. This is a neutral mutation because both glycine and alanine are nonpolar amino acids. |
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Silent mutation
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Silent mutations Previous Page, Next Page , Top of Page Silent mutations are a type of substitution mutations in which a base substitution in the DNA template results no change in the amino acid. This is because the substitution simply resluts in another codon for the same amino acid. Thus these mutations are silent, since you cannot detect them by looking at the protein's sequence of amino acids. |
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Nonsense Mutation
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Nonsense mutations Previous Page, Next Page , Top of Page A nonsense mutation is a mutation that replaces a codon for an amino acid with one of the three stop codons. This cause an early termination of transcription resulting in a shortened and usually non fiunctional polypeptide. |
