Lesson 2: Mutation (II)

2. Gene Mutation/Point mutation

Gene mutation is a change in sequence of nucleotide bases of the DNA. It occurs at a single locus on a chromosome. There are 4 types of gene mutation:

(a) Base Insertion (addition) 

Insertions are mutations in which extra base pairs are inserted into a new place in the DNA. They are usually caused by transposable elements, or errors during replication of repeating elements (e.g. AT repeats). Insertions in the coding region of a gene may alter splicing of the mRNA (splice site mutation), or cause a shift in the reading frame (frameshift), both of which can significantly alter the gene product. Insertions can be reverted by excision of the transposable element. Effects of insertion/deletion of 3 nucleotide bases are less serious than insertion of 1/2 nucleotide bases. This is due to no shifting of DNA base sequence after the insertion point.  Only 1 amino acid residue is added or deleted in the new polypeptide chain.

Sorry...I cant find any pic on the internet so I'll use my method to describe what is base insertion:

    CTGGAG

CTGGTGGAG

• As what you can see, there is a base(TGG) adding to the base sequence which alter the DNA sequence but it is less serious.

(b) Base Substitution

A substitution is a mutation that one base is replaced by another base (i.e., a change in a single "chemical letter" such as switching an A to a G). If a purine (A , G) replaces a purine or pyrimidine (C,T) replaces pyrimidine, it is called Transition Substituition. If a purine replaces a pyrimidine or vice versa, this is a Transverse Substituition. Substituition mutations are usually missence mutations. The new nucleotide base alters one genetic code to a different code.

CTGGAG
CTGGGG

The change of a single nucleotide--can also change a codon so that a different protein is specified, a non-synonymous change. This is called a missense mutation, since the wrong amino acid is specified. The protein coded by the gene therefore has a change to a single amino acid. This often has no significant effect on the protein, as most can tolerate a few amino acid changes without their biological function changing. On the other hand, sometimes a missense mutation does have a significant effect. Many Fanconi Anemia mutations are missense mutations.

For example, sickle cell anemia is caused by a substitution in the beta-hemoglobin gene, which alters a single amino acid in the protein produced.

ATG   GAA   GCA   CGT                       Change to                 ATG   GAC   GCA   CGT 

MET   GLU   Ala      Gly                          Change to                 MET   Asp     Ala      Gly

In nonsense mutation, new base changes a codon that encodes a particular amino acid into one of the stop codon. Translation of mRNA is terminated and a shorter or nonfunctional protein is produced.

ATG   GAA   GCA   CGT                    Change to                 ATG   TAA   GCA   CGT 

MET   GLU   Ala      Gly                       Change to                 MET   STOP

Silent mutation does not alter polypeptide formed because mutated codon still encodes for the same amino acid. It can only detected by sequencing the nucleotide bases of the gene.

Sickle-cell anaemia

Substitution of a base thymine by adenine in the gene that codes for the beta polypeptide chain. This changes triplet code ( CTT( for glutamic acid) CAT (valine). This causes alteration of the ß-polypeptide chain. In active body tissues where oxygen concentration is low, altered ß-chains tend to stick together forming long fibres and abnormal haemoglobin molecules crystalline. The red blood cells are pulled into sickle shape. These cells have a lower affinity to bind oxygen and are easily trapped within capillaries causing a reduction in oxygen supply to tissues and damage to organs such as the kidney.