Protein Structure & Mutations (HL IB Biology)

• A gene mutation is a change in the sequence of bases in a DNA molecule; this may result in a new allele
  • Mutations occur all the time and occur randomly
  • Mutations are copying errors that take place when DNA is replicated during S phase of interphase
• As the DNA base sequence determines the sequence of amino acids that make up a polypeptide, mutations in a gene can sometimes lead to a change in the polypeptide for which the gene codes
• Most mutations are harmful or neutral (have no effect) but some can be beneficial
• Inheritance of mutations:
  • Mutations present in normal body cells are not inherited; they are eliminated once the affected cells die
  • Mutations within gametes are inherited by offspring, so can lead to heritable genetic conditions
• Point mutations are mutations where one base in the DNA sequence is altered; this can result in a changed amino acid at this location

Example of a point mutation: sickle cell disease

• A small change to a gene can have serious consequences for an organism
• Sickle cell disease is a genetic disorder caused by a single point mutation within the gene that codes for the alpha-globin polypeptide in haemoglobin (Hb)
  • Most humans have the allele Hb^A
  • The mutation results in a new allele Hb^S

The sickle cell mutation

• Within the haemoglobin gene a point mutation changes the DNA triplet GAG to GTG on the coding strand
• The resulting DNA triplet (CAC) on the template strand is transcribed into the mRNA codon GUG, instead of GAG
• During translation the amino acid valine (Val) replaces the original amino acid glutamic acid (Glu)
  • This occurs at the sixth position of the polypeptide

Sickle cell anaemia point mutation diagram

A base substitution on the DNA molecule results in a change in the amino acid at position 6 of the haemoglobin polypeptide, altering the overall structure and function of the protein

The effects

• The protein haemoglobin S is produced instead of haemoglobin A; this causes a distortion in the shape of red blood cells, resulting in a sickle shape
• Sickle-shaped red blood cells:
  • Have a limited oxygen-carrying capacity
  • Block the capillaries and limit the flow of normal red blood cells
• People with sickle cell anaemia suffer from acute pain, fatigue and anaemia
• There is a correlation between the global distribution of sickle cell disease and malaria
  • In areas with increased malaria cases there is an increased frequency of sickle cell alleles; this is thought to be due to increased resistance to the malaria parasite in individuals with the Hb^S allele

Sickled cells diagram

Sickled cells can block the flow of blood through the capillaries, restricting oxygen supply to the tissues

• You will cover more on mutations later in the course; see this link