8 Gene Mutations (DIY)

• Define Gene Mutation

  • A gene mutation arises as a result of a change in the sequence of nucleotides/ bases in the DNA of a gene
• Causes of Gene mutations

  • SPONTANEOUS - arise from errors in DNA replication or spontaneous damage to DNA
  • INDUCED - due to exposure to a mutagen (chemical or physical agent that interacts with DNA to cause a mutation)
  • Ionising Radiation (UV light, gamma radiation, carcinogens etc.)
  • Some viruses
• What happens when a gene mutation occurs?

  • A change in the sequence of nucleotides in DNA leads to a change in the sequence of codons in mRNA → change in sequence of amino acids in the resulting polypeptide chain → changes the 3D conformation of the protein → affects function → affects characteristics (phenotype)
• Outcome of genetic mutation

  • Genetics mutations can manifest as a disease in the organism
  • Can result in inheritable diseases
  • Occurs when the germline mutations occur in the gametes (sex cells) or germ cells of the gonads)
  • Somatic mutations occur in somatic cells of the body and would not be passed on to offspring
• Types of Gene Mutations

  1. Substitution
  2. Insertion/ Deletion
  3. Inversion
• Type of Mutation terms

  1. Silent Mutation
  2. Nonsense Mutation
  3. Missense Mutation (Conservative/ Non-conservative)
• Point Mutation


  A gene mutation that results in a change in just a single base
• Substitution Mutation

  • Occurs when one or more nucleotides (or base pairs) is/ are replaced by another nucleotide (or base pair)
  • Most common type of gene mutation
  • May not be as serious as deletion or addition as the replacement of a nucleotide may not necessarily affect the function of the protein as much (furthermore since it occurs on both DNA strands)
• Why do substitution mutations not necessarily affect protein function as much as other types of mutations? (Reason 1)

  • The genetic code is DEGENERATE (same amino acid can be coded for by more than 1 codon)
  • Certain codons that differ at the 3rd base all code for the same amino acid → amino acid sequence is not affected as a result of any substitution mutation at the third base of a codon
  • Known as a SILENT mutation as the amino acid being coded for is not changed
• Why do substitution mutations not necessarily affect protein function as much as other types of mutations? (Reason 2)

  • Even though the substitution mutation results in a different amino acid being coded for, the ‘new’ amino acid has an R group which has similar chemical properties to the amino acid it had replaced
  • Thus, mutations may not affect the folding of the polypeptide → the function of the protein is unaffected as both amino acids have R-groups with similar properties
  • Known as CONSERVATIVE MISSENSE mutations
  • VS R-groups with dissimilar chemical properties → non-conservative missense
• • How can substitution mutations severely disrupt protein function?
  • Introduction of a premature stop codon (UAG, UAA or UGA) in mRNA strand
  • Non-sense mutation give rise to truncated (shortened) protein product that is highly likely to be non-functional
• Insertion/ Deletion Mutations (Definition)

  • Insertion/ addition: occurs when one or more nucleotides are inserted/ added into a gene sequence
  • Deletion: occurs when one or more nucleotides are removed from a gene sequence
• Insertion/ Deletion Mutation

  • BOTH often results in a different sequence of amino acids to be encoded and thus production of a non-functional protein
  • Ribosomes begin to read incorrect triplets from the point of insertion or deletion
  • The sequence of bases in each codon downstream from the point of mutation are not read correctly
  • Known as frameshift mutations → more severe in their consequences than any other type of mutation
  • Occurs because the genetic code is non-overlapping and continuous so the ribosome just reads the sequence of bases as they are
• What happens if a segment of three nucleotides were added/ deleted?

  • Would not result in a frameshift mutation since the reading frame of the original sequence is conserved
  • Overall base sequence is not changed because codons can still be read correctly after the point of mutation
  • Will simply result in one extra or one less amino acid in the resulting polypeptide chain → results in a loss or slight modification of the protein’s 3D conformation, depending on how critical this amino acid is
  • If a stop codon is introduced → likely a non-functional protein
• Inversion Mutation (Definition)

  • Inversion: occurs when a segment of nucleotide sequence separates from the allele and rejoins at the original position but it is inverted and the sequence is now reversed
• Inversion Mutation

  • The length of gene segment being inverted is highly variable → resulting effects on the amino acid sequence depend on the length of inversion
• • What happens when a segment of 3 nucleotides were inverted
  • Inversion of a segment of 3 bases would not result in any change in the reading frame
  • Frameshift mutation does not occur → inverted codon would code for a different amino acid, with varying effects depending on the type of amino acid being changed
  • If a stop codon is introduced → would be a nonsense mutation as translation terminates prematurely, resulting in a truncated polypeptide chain → likely a non-functional protein
• Haemoglobin

  • Abundant in red blood cells → serves the crucial role of transporting oxygen from the lungs to respiring tissue all over the body
  • Structural features: (of normal adult haemoglobin - HbA)
  • Globular protein, roughly spherical in shape
  • Quaternary structure of 4 polypeptide chains: 2 alpha-globin & 2 beta-globin
  • Coded for by 2 different genes found on different chromosomes
  • A mutation in one globin gene is unlikely to affect the other
  • One prosthetic haem group attached to each globin chain
• Sickle Cell Anaemia

  • The disease is caused by a single nucleotide substitution mutation in the gene which codes for the beta-globin chain
  • Is a homozygous recessive disorder
  • Only individuals with 2 copies of the mutant form of the gene have sickle cell
  • Heterozygous individuals having only 1 copy of the mutant and 1 copy of the normal form of the gene are said to have the sickle cell trait (carriers)
• Impact of Mutation in Haemoglobin (1)

  1. Change in sequence of amino acids in polypeptide chain

  • Due to the point mutation, the 6th codon in the mRNA is changed from GAG to GUG
  • Amino acid coded for by the new codon is changed from glutamate to valine in the beta-globin chain
  • Forms a variant sickle cell haemoglobin (HbS)
• Impact of Mutation in Haemoglobin (2)

  1. Change in properties of sickle cell haemoglobin (HbS)

  • The R group of glutamate is charged and hydrophilic whereas that of valine is non-polar and hydrophobic
  • The change in amino acid results in an exposed hydrophobic patch/ region on the outside of the beta-globin chain is formed when oxygen level is low
• Impact of Mutation in Haemoglobin (3)

  1. Change in shape of the red blood cell

  • Hydrophobic region can stick to the hydrophobic region of an adjacent haemoglobin molecule’s beta-globin chain via hydrophobic interactions
  • Causes polymerisation of HbS into abnormal rigid rod-like fibres that distort the normal biconcave shape of the red blood cell into sickle shape at low oxygen level
• Sickle-Cell Anaemia Effects (1)

  1. Sickle RBCs are more fragile causing them to break more easily

  • Are actively destroyed in the spleen
  • Results in the shortage of RBCs and poor oxygen transport
  • Can result in:
  • Anaemia, breathlessness, and physical weakness
  • Heart failure (heart needs to work harder)
  • Weakness, lack of energy (insufficient ATP due to reduced cellular respiration)
• Sickle-Cell Anemia Effects (2)

  1. Sickle-shaped RBC are less flexible than normal RBCs

  • May get lodged in small blood vessels/ capillaries and hence interfere with blood circulation
  • Can result in:
  • Depriving organs of oxygen
  • Severe pain due to many localised blockages resulting in death of surrounding tissue
  • Damage to organs especially those with numerous fine capillaries (spleen and lungs etc.)