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Mutation is a permanent change in the sequence of DNA that makes up a gene is known as mutation. Mutations may vary in size from single DNA base to a large fragment of a chromosome. Let us focus on different types of mutation, starting with substitution.
Substitution
A type of mutation wherein a single nucleotide is exchanged for or substituted with a different nucleotide that alters the amino acid sequence in translation rendering ineffective newly synthesized protein is known as substitution. One example of is substitution of purine with another purine (A → G) or a pyrimidine with another pyrimidine (C → T). This type of substitution is also known as transition. Another kind is transversion in which a purine with pyrimidine or a pyrimidine with a purine is substituted. Mutations due to substitution replaces one base with another. Due to redundancy in genetic code some substitutions may not pose any effect at all. As, for example a uracil substitution for a cytosine in the CCU codon does not impart any effect on the protein synthesised as both CCC and CCU code for proline. On the other hand, depending on the region of substitution in the amino acid chain a substitution replacing the amino acid with another may vary widely in the effect that might occur.
For example a substitution producing AUG (the stop codon) is the most serious one as it will prematurely end an amino acid chain. Changes that cause a lesser effect on the configuration of protein does not dramatically affect the protein function. Mutation in an individual that occurs due to single base substitution may have significant consequences. As, for example, sickle cell anemia, which is a serious disease occurs due to mutation from single base substitution. A point mutation of the β- globin gene in codon 6 results in the substitution of glutamic acid by valinethereby causing sickle cell anemia. β-globin is an important component of haemoglobin (HbA). Amino-acid substitution results in HbS type of haemoglobin, with different properties from the normal HbA. In certain conditions like low oxygen tension following exercise or lesser oxygen content of the atmosphere, the following changes occur:
(1) Agglutination of the hemoglobin, forming insoluble rod-shaped polymers;
(2) Distorted sickle –shaped red blood cells
(3) Rupture of the sickle-shaped cells, causing haemolytic anemia;
(4) Blockage of capillaries due to sickle shaped cells, causing interference with the blood flow to the organs.
Another disease caused by substitution mutation is thalassemia. In this case the in codon 39 a single base substitution of C by U form of a stop signal UAG in place of glutamate and a shortened globin chain having only 39 amino acids in the β-globin chain of protein instead of the normal 146. This protein is not functionally active getting equivalent to absence of β-globin thereby causing medical symptoms of thalassemia.