Point mutation

In biology, a point mutation is a gene mutation when only a single nucleobase is affected by the change .

Forms of point mutation

Reading frame is retained

Due to the degenerate property (redundancy) of the genetic code , such a point mutation can have no consequences. Degeneracy here means that an amino acid can be encoded by several codons . 61 coding base triplets are available for the 20 amino acids (3 base triplet combinations are non-coding). If the point mutation turns the original codon into a codon that codes for the same amino acid, the result is the same protein as with the original codon.

substitution

If one base of the DNA is exchanged for another in a point mutation , this process is called substitution. If this exchange takes place in a coding region, a modified mRNA is transcribed and causes the incorporation of a different amino acid , which leads to a modified protein which, depending on the location of the mutation and substituted amino acid, may not or no longer carry out its tasks completely can. A well-known example of a point mutation in humans is sickle cell anemia . Improvement in the polypeptide is just as possible, although less likely. An example of this would be an increased substrate conversion of an enzyme.

Different types of point mutations. Transitions are shown with hollow arrows, transversions with filled in ones.

There are two types of substitution in point mutation:

Transition : substitution of a purine - for another purine base or a pyrimidine - for another pyrimidine base.
Transversion : substitution of a purine for a pyrimidine base or vice versa.

For coding sequences , the substitution can be divided into the following categories:

Functional, d. H. they have an effect on the formation of proteins:
- nonsense mutation: encodes a stop in translation
- missense mutation or non-synonymous mutation (mutation that changes meaning): codes for a different amino acid
- readthrough mutation: a stop codon is encoded as an amino acid
Non-functional, i.e. H. due to the redundancy of the genetic code , the same amino acid is still coded:
- silent mutation or synonym ( silent mutation ): codes for the same amino acid

It can either be a "missense" mutation (meaning changing mutation), i.e. the replacement of an amino acid during translation , or a "nonsense " mutation (meaning distorting mutation), which creates a stop codon . In addition, “nonsense” mutations in introns can cause splicing errors . Here lead "nonsense" mutations not necessarily in a single individual to an eye-catching phenotype , but can evolutionary periods still be detrimental. As a third possibility, it can also be a silent (silent) mutation or neutral mutation in which a base has been changed but the same amino acid is still encoded. This is entirely possible because, due to the degeneracy of the genetic code, there are several coding options for some amino acids. However, recent research has shown that silent mutations can also cause disease. The reason for this is that with certain silent mutations (on the way from the cell nucleus to the ribosome) the mRNA folds differently than usual , with the result that it is hardly translated or that it is translated too much.

Shifts in the reading frame

A point mutation can be worse if a base is completely removed or a new one is added. Here, the mRNA strand behind the mutation loses its original meaning because it is shifted to the left or right ( frameshift ). As a result, the translated protein later has a completely different structure. Its original function is usually lost.

Deletion

A deletion is the loss of a base. The following bases move against the reading direction, which shifts the reading frame of the following codon in this same direction.

Insertion

An insertion is the gain of a base. The following bases move up in the reading direction, which shifts the reading frame of the following codon in this same direction.

example

The frameshift ( frameshift ) can be explained by a small example. When you get the sentence

ICH MAG NUR EIN EIS

considered, it makes sense. Each word consists of three letters (triplets). Similarly, the information is also available on a gene , here the bases are always combined into so-called base triplets . If a letter is now added - but attention is still paid to the fact that a three-letter word sentence is to be formed - this information disappears. In this example, the letter X is added after the word “I”. This corresponds to an insertion .

ICH XMA GNU REI NEI S

If the letter M is deleted after the word “I” - which is tantamount to a deletion - but the three-letter word rule remains valid, the sentence no longer makes sense from the word ICH either.

ICH AGN URE INE IS

The situation is similar when a base is added to a gene. The genetic information can no longer be read off meaningfully.

Experimental use

With an understanding of point mutations, it was possible to develop the Ames test , which detects the presence of mutagens .

Web links

WE Lönnig: point mutations

Individual evidence

Jump up ↑ Bryndis Yngvadottir, Yali Xue, Steve Searle, Sarah Hunt, Marcos Delgado: A Genome-wide Survey of the Prevalence and Evolutionary Forces Acting on Human Nonsense SNPs . In: The American Journal of Human Genetics . tape 84 , no. 2 , February 13, 2009, p. 224–234 , doi : 10.1016 / j.ajhg.2009.01.008 ( sciencedirect.com [accessed October 26, 2017]).

[1] Jump up ↑ Bryndis Yngvadottir, Yali Xue, Steve Searle, Sarah Hunt, Marcos Delgado: A Genome-wide Survey of the Prevalence and Evolutionary Forces Acting on Human Nonsense SNPs . In: The American Journal of Human Genetics . tape 84 , no. 2 , February 13, 2009, p. 224–234 , doi : 10.1016 / j.ajhg.2009.01.008 ( sciencedirect.com [accessed October 26, 2017]).