2.14 Mutations

• A gene mutation is a change in the sequence of bases in a DNA molecule
• Mutations may result in an altered polypeptide; as the DNA base sequence of a gene determines the sequence of amino acids that make up a polypeptide, mutations in a gene can sometimes lead to a change in the polypeptide that the gene codes for
• Mutations occur spontaneously during DNA replication
• There are different ways that a mutation in the DNA base sequence can occur, e.g.
  • Substitution
  • Insertion
  • Deletion
• Substitution, insertion, and deletion mutations are all examples of point mutation; mutations that involve a change in the DNA base sequence at a single location
• Other types of mutation can affect entire genes or entire chromosomes
  • Genes can be replicated or lost
  • Chromosomes can be divided unequally during meiosis, resulting in cells with extra or missing chromosomes

Substitution of nucleotides 

• A mutation that occurs when a base in the DNA sequence is randomly swapped for a different base
• A substitution mutation will only change the amino acid for the triplet in which the mutation occurs, and will have no impact on triplets located elsewhere in the gene
• Substitution mutations include
  • Silent mutations
    • The mutation does not alter the amino acid sequence of the polypeptide; this is due to the degenerate nature of the genetic code
  • Missense mutations
    • The mutation alters a single amino acid in the polypeptide chain, e.g. sickle cell anaemia is caused by a single substitution mutation changing a single amino acid in the haemoglobin protein
  • Nonsense mutations
    • The mutation creates a premature stop codon, causing the polypeptide chain produced to be incomplete and therefore affecting the final protein structure and function, e.g. cystic fibrosis can be caused by a nonsense mutation
      • Note that a stop codon provides a signal for the cell to stop translation of the mRNA molecule into an amino acid sequence

Substitution mutations involve swapping one nucleotide for another

Insertion of nucleotides

• A mutation that occurs when a nucleotide is randomly inserted into the DNA sequence is known as an insertion mutation
• An insertion mutation changes the amino acid that would have been coded for by the original base triplet, as it creates a new, different triplet of bases
  • Remember that every group of three bases in a DNA sequence codes for an amino acid
• An insertion mutation also has a knock-on effect on other base triplets by changing the triplets further on in the DNA sequence
  • This means that insertion mutations cause what is known as a frameshift mutation; they don't only change the triplet where the insertion has occurred, but every triplet downstream of the insertion
• This may dramatically change the amino acid sequence produced from this gene and therefore the ability of the polypeptide to function

Insertion mutations occur when a new nucleotide is added into a base sequence

Deletion of nucleotides

• A mutation that occurs when a nucleotide is randomly deleted from the DNA sequence
• Like an insertion mutation, a deletion mutation changes the triplet in which the deletion has occurred, and also changes every group of three bases further on in the DNA sequence
  • This is known as a frameshift mutation
• This may dramatically change the amino acid sequence produced from this gene and therefore the ability of the polypeptide to function

• Most mutations do not alter the polypeptide or only alter it slightly so that its appearance or function is not changed
  • This is possible because the genetic code is degenerate; the base sequence can be changed without necessarily altering the amino acid
• However, a small number of mutations code for a significantly altered polypeptide 
  • A mutation changes the DNA base sequence
  • One or many amino acids in the primary structure of a protein is altered
  • Different bonds form in the secondary and tertiary structures of the protein
  • The final 3D structure of the protein is altered

• Very rarely this can give rise to a protein that provides an organism with an advantage, e.g. resistance to an antibiotic, or the ability to digest a new type of food
  • Mutations that provide an advantage can drive the process of evolution by causing natural selection to occur
    • Individuals with an advantage are more likely to survive and reproduce
    • The advantageous mutation is more likely to be passed on
    • The mutation becomes more common in the population

• More often, mutations that affect polypeptide structure are likely to be harmful, affecting the ability of proteins to perform their function, e.g.
  • In cystic fibrosis, a membrane channel protein no longer functions
    • A fault in the CFTR gene leads to production of non-functional chloride channels, reducing the movement of water by osmosis into cell secretions
    • This results in the production of thick, sticky mucus in the air passages, the digestive tract and the respiratory system
  • In sickle-cell disease, the haemoglobin protein no longer functions
    
    • Sickle-cell disease is caused by a single substitution mutation that causes haemoglobin proteins to clump together
    • This affects the shape of red blood cells, preventing easy blood flow and causing severe pain and problems with blood supply to important organs

Sickle cell disease is caused by a single substitution mutation that changes one amino acid in the haemoglobin protein

• Mutations in the genes that are involved with cell division can lead to uncontrolled cell division and the development of tumours that can become cancerous
• Mutations that occur in the gametes, or sex cells, can be passed on to future generations, meaning that every cell in the body of an organism's offspring will contain the mutation
• Mutagens can increase the likelihood of a mutation occurring, e.g.
  • Ionising radiation
  • X-rays
  • Some chemicals