Point mutation
Encyclopedia
A point mutation, or single base substitution, is a type of mutation
that causes the replacement of a single base nucleotide
with another nucleotide of the genetic material, DNA
or RNA
. Often the term point mutation also includes insertions or deletions of a single base pair. One can categorize point mutations as follows:
Transition mutations are about an order of magnitude more common than transversions. Point mutations can also be categorized functionally:
For example, sickle-cell disease
is caused by a single point mutation (a missense mutation) in the beta-hemoglobin
gene
that converts a GAG codon into GUG, which encodes the amino acid
valine
rather than glutamic acid
. This is an example of a non-conservative (missense) mutation.
Point mutations that occur in non-coding sequences are most often without consequences, although there are exceptions. If the mutated base pair is in the promoter sequence of a gene, then the expression of the gene may change. Also, if the mutation occurs in the splicing site of an intron
, then this may interfere with correct splicing of the transcribed pre-mRNA.
Sometimes the term point mutation is also used to describe insertions
or deletions of a single base pair (which has more of an adverse effect on the synthesized protein due to the nucleotides' still being read in triplets, but in different frames: a mutation called a frameshift mutation
).
A "point mutant" is an individual which is affected by a point mutation.
s that occur during DNA replication
. The rate of mutation may be increased by mutagen
s. Mutagens can be physical, such as radiation from UV rays, X-ray
s or extreme heat, or chemical (molecules that misplace base pairs or disrupt the helical shape of DNA). Mutagens associated with cancers are often studied to learn about cancer and its prevention.
There is a systematic difference in rates for transition
s (Alpha) and transversion
s (Beta).
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
that causes the replacement of a single base nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
with another nucleotide of the genetic material, DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
or RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
. Often the term point mutation also includes insertions or deletions of a single base pair. One can categorize point mutations as follows:
- transitions: replacement of a purinePurineA purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
base with another purinePurineA purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
or replacement of a pyrimidinePyrimidinePyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...
with another pyrimidine - transversions: replacement of a purine with a pyrimidine or vice versa.
Transition mutations are about an order of magnitude more common than transversions. Point mutations can also be categorized functionally:
- nonsense mutationNonsense mutationIn genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product. It differs from a missense mutation, which is a point mutation...
s: code for a stop, which can truncate the proteinProteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of... - missense mutationMissense mutationIn genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional...
s: code for a different amino acid - conservative mutations: result in an amino acid change; however, the properties of the amino acid remain the same (e.g. hydrophobic, hydrophilic, etc).
- non conservative mutations: result in an amino acid change that has different properties than the wild type.
- silent mutationSilent mutationSilent mutations are DNA mutations that do not result in a change to the amino acid sequence of a protein. They may occur in a non-coding region , or they may occur within an exon in a manner that does not alter the final amino acid sequence...
s: code for the same amino acid
For example, sickle-cell disease
Sickle-cell disease
Sickle-cell disease , or sickle-cell anaemia or drepanocytosis, is an autosomal recessive genetic blood disorder with overdominance, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various...
is caused by a single point mutation (a missense mutation) in the beta-hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
that converts a GAG codon into GUG, which encodes the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
rather than glutamic acid
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
. This is an example of a non-conservative (missense) mutation.
Point mutations that occur in non-coding sequences are most often without consequences, although there are exceptions. If the mutated base pair is in the promoter sequence of a gene, then the expression of the gene may change. Also, if the mutation occurs in the splicing site of an intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
, then this may interfere with correct splicing of the transcribed pre-mRNA.
Sometimes the term point mutation is also used to describe insertions
Insertion (genetics)
In genetics, an insertion is the addition of one or more nucleotide base pairs into a DNA sequence. This can often happen in microsatellite regions due to the DNA polymerase slipping...
or deletions of a single base pair (which has more of an adverse effect on the synthesized protein due to the nucleotides' still being read in triplets, but in different frames: a mutation called a frameshift mutation
Frameshift mutation
A frameshift mutation is a genetic mutation caused by indels of a number of nucleotides that is not evenly divisible by three from a DNA sequence...
).
A "point mutant" is an individual which is affected by a point mutation.
Causes
Point mutations may arise from spontaneous mutationMutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s that occur during DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
. The rate of mutation may be increased by mutagen
Mutagen
In genetics, a mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are therefore also likely to be carcinogens...
s. Mutagens can be physical, such as radiation from UV rays, X-ray
X-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
s or extreme heat, or chemical (molecules that misplace base pairs or disrupt the helical shape of DNA). Mutagens associated with cancers are often studied to learn about cancer and its prevention.
There is a systematic difference in rates for transition
Transition (genetics)
In genetics, a transition is a point mutation that changes a purine nucleotide to another purine or a pyrimidine nucleotide to another pyrimidine . Approximately two out of three single nucleotide polymorphisms are transitions....
s (Alpha) and transversion
Transversion
In molecular biology, transversion refers to the substitution of a purine for a pyrimidine or vice versa. It can only be reverted by a spontaneous reversion. Because this type of mutation changes the chemical structure dramatically, the consequences of this change tend to be more drastic than those...
s (Beta).