Gene Mutations - Substitution (Replacement) Mutations

• Mutation is a sudden, heritable change in the genetic material of an organism.
• Gene mutation is a change in the nucleotide sequence of a single gene.
• Substitution mutation is a type of point mutation where one nucleotide base is replaced by another in a DNA segment (gene).
• Because only one base pair is altered, substitution mutations are grouped under point mutations in school-level genetics.
• A single base substitution can be silent, produce a mild effect, or cause a major change in phenotype, depending on the position and role of the affected amino acid.

• DNA bases are of two types: purines (adenine A, guanine G) and pyrimidines (cytosine C, thymine T).
• Transition mutation: one purine is replaced by another purine (A ↔ G) or one pyrimidine by another pyrimidine (C ↔ T).
• Transversion mutation: a purine is replaced by a pyrimidine or a pyrimidine by a purine (A ↔ T, A ↔ C, G ↔ T, G ↔ C).

A-B- Base pair replacements involved in transitions (A) and transversions (B)

• Base substitution changes the codon in mRNA, which may change the amino acid inserted into the polypeptide chain.
• If the amino acid change alters protein structure or function significantly, the phenotype can change and a disorder may appear.

• Sickle cell anaemia is a standard example of a harmful substitution (point) mutation affecting haemoglobin.
• A single point mutation in the β-globin gene changes one codon, leading to replacement of glutamic acid by valine at position 6 of the β chain.
• The altered haemoglobin (HbS) tends to polymerise under low oxygen, making red blood cells sickle-shaped and less flexible.
• Sickle-shaped cells can block capillaries, reduce oxygen supply and cause clinical symptoms.

• Substitution mutation is a type of point mutation where one nucleotide base in a gene is replaced by another.
• Two types: transition (purine→purine or pyrimidine→pyrimidine) and transversion (purine↔pyrimidine).
• Somatic mutations affect body cells only and are not inherited; germline mutations occur in gametes and can be passed to offspring.
• A single base change can alter an amino acid in a protein, which may significantly change its function and cause a disorder.
• Sickle cell anaemia is the key example - a point mutation in the β-globin gene replaces glutamic acid with valine, producing abnormal HbS and sickle-shaped RBCs.