6.1.1

• Mutation - random change to the genetic material

  • mutation may occur spontaneously during DNA replication before cell division

  →certain chemicals such as tar in tobacco smoke, and ionising radiation such as UV light, X-rays + gamma rays, may be mutagenic
• Types of genetic mutation

  structure of DNA makes it fairly stable + resistant to corruption of the genetic information stored within it

  → errors may occur, however, during the replication of DNA molecule

  • mutations associated with mitotic divisions are somatic mutations + not passed to offspring

  → may be associated with the development of cancerous tumours

  • mutations associated with meiosis + gamete formation may be inherited by offspring
  • gene mutations may affect protein production + function
• two main classes of DNA mutation:

  • Point mutation: one base pair replaces another (substituted)
  • insertion or deletion (indel) mutation: one or more nucleotides are inserted or deleted from a length of DNA

  → may cause a frameshift
• Point mutations

  genetic code consists of nucleotide base triplets within the DNA

  • during transcription of a gene, this code is copied to a length of mRNA as codons, complementary to the base triplets on the template strand of the length of DNA is therefore a copy of the sequence of base triplets on gene (coding strand on DNA)

  three types of point mutation:

  • silent
  • missense
  • nonsense
• Silent Mutations

  all amino acids involved in protein synthesis, apart from methionine, have more than one base triplet code

  • this reduces the effect of point mutations,as they don’t always cause a change to the sequence of amino acids in a proteins

  → often called redundancy or degeneracy of the genetic code

  • a point mutation involving a change to a base triplet, where the triplet still codes for the same amino acid, is a silent mutation

  → the primary structure of the protein, + therefore secondary + tertiary structure, is not altered

  figure 2

  
• Missense Mutations

  a change to the base triplet sequence that leads to a change in the amino acid sequence in a protein is a missense mutation

  • within a gene, such a point mutation can have a significant effect on the protein produced

  → the alteration to the primary structure leads to a change to tertiary structure, altering its shape + prevent doing its function

  figure 3

  
• Missense example

  • Sickle cell anaemia results from missense mutation on the sixth base triplet for the beta-polypeptide chains of haemoglobin: the amino acid valine, instead of glutamic acid , is inserted at this point

  → this results in deoxygenated haemoglobin crystallising within erythrocytes, causing them to become sickle shaped, blocking capillaries + depriving tissues of oxygen
• Nonsense Mutations

  a point mutation may alter a base triplet, so that it becomes a termination (stop) triplet

  • this particularly disruptive mutation results in a truncated protein that will not function
  • this abnormal protein will most likely to be degraded within the cell

  → the genetic disease Duchenne muscular dystrophy is the result of a nonsense mutation

  figure 4

  
• Indel mutations

  both insertions + deletions cause a frameshift
• Insertions and deletions

  • if nucleotide base pairs, not in multiple of three, are inserted in the gene or deleted from the gene, because the code is non-overlapping + read in groups of three bases, all the subsequent base triplets are altered

  → this is a frameshift

  • Translation of mutated gene mRNA results in disrupted amino acid sequence due to frameshift.
  • Primary and tertiary protein structures are significantly altered.
  • Protein loses its normal function.
  • Abnormal protein is rapidly degraded within the cell.

  figure 5

  
• Insertions + deletions 2

  some forms of thalassaemia, a haemoglobin disorder, result from frameshifts due to deletions of nucleotide bases

  • insertions or deletion of a triplet of base pairs result in the addiction or loss of an amino acid, and not in a frameshift
• Expanding triple nucleotide repeats

  some genes contain a repeating triplet such as -CAG CAG CAG-

  in an expanding triple nucleotide repeat the number of CAG triplets increases at meiosis + again from generation to generation

  Huntington disease results from an expanding triple nucleotide repeat

  • if the number of repeating CAG sequences goes above a certain critical number, then the person with the genotype will develop the symptoms of Huntingdon disease later in life
• Not all mutations are harmful

  • Mutations can be beneficial, driving evolution through natural selection by producing new alleles

  -> example: The mutation for blue eyes may be harmful in high-sunlight areas (risk of cataracts) but advantageous in temperate zones (better vision in low light)

  • early humans in Africa had dark skin with high melanin to protect against sunburn and skin cancer
  • in temperate regions, paler skin was advantageous for producing vitamin D in low sunlight
  • fair-skinned individuals were selected as vitamin D protects against rickets, heart disease, and cancer
• some mutations appear to be neutral, being neither beneficial nor harmful, such as those that in humans cause:

  • inability to smell certain flowers, including freesias + honeysuckle
  • differently shaped ear lobes

  not all genes code for polypeptides, some code for RNA that regulates the expression of other genes

  some apparently silent mutations in such genes could be harmful by incorrectly regulating the expression of another gene