Genetic Mutations (AQA A Level Biology)

• A gene mutation is a change in the sequence of base pairs in a DNA molecule that may result in an altered polypeptide
• Mutations occur continuously and spontaneously
  • Errors in the DNA often occur during DNA replication

• As the DNA base sequence determines the sequence of amino acids that make up a protein, mutations in a gene can sometimes lead to a change in the polypeptide that the gene codes for
• Most mutations do not alter the polypeptide or only alter it slightly so that its structure or function is not changed (as the genetic code is degenerate)
• Mutations in the DNA base sequence can occur due to the insertion, deletion or substitution of a nucleotide or due to the inversion, duplication or translocation of a section of a gene

Insertion of nucleotides 

• A mutation that occurs when a nucleotide (with a new base) 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
  • This is because every group of three bases in a DNA sequence codes for an amino acid

• An insertion mutation also has a knock-on effect by changing the triplets (groups of three bases) further on in the DNA sequence
• This is sometimes 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

An example of an insertion mutation

Deletion of nucleotides 

• A mutation that occurs when a nucleotide (and therefore its base) is randomly deleted from the DNA sequence is known as a deletion mutation
• Like an insertion mutation, a deletion mutation changes the amino acid that would have been coded for
• Like an insertion mutation, a deletion mutation also has a knock-on effect by changing the groups of three bases further on in the DNA sequence
• This is sometimes 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

Substitution of nucleotides 

• A mutation that occurs when a base in the DNA sequence is randomly swapped for a different base is known as a substitution mutation
• Unlike an insertion or deletion mutation, a substitution mutation will only change the amino acid for the triplet (group of three bases) in which the mutation occurs; it will not have a knock-on effect
• Substitution mutations can take three forms:
  • Silent mutations – the mutation does not alter the amino acid sequence of the polypeptide (this is because certain codons may code for the same amino acid as the genetic code is degenerate)
  • Missense mutations – the mutation alters a single amino acid in the polypeptide chain (sickle cell anaemia is an example of a disease caused by a single substitution mutation changing a single amino acid in the sequence)
  • Nonsense mutations – the mutation creates a premature stop codon (signal for the cell to stop translation of the mRNA molecule into an amino acid sequence), causing the polypeptide chain produced to be incomplete and therefore affecting the final protein structure and function (cystic fibrosis is an example of a disease caused by a nonsense mutation, although this is not always the only cause)

An example of a substitution mutation

Inversion within a gene section

• Usually occurs during crossing-over in meiosis
• The DNA of a single gene is cut in two places
• The cut portion is inverted 180° then rejoined to the same place within the gene
• The result is a large section of the gene is 'backwards' and therefore multiple amino acids are affected
• Inversion mutations frequently result in a non-functional protein
  • In some cases, an entirely different protein is produced

• The mutation is often harmful because the original gene can no longer be expressed from that chromosome
  • If the other chromosome in the pair carries a working gene the effect of the mutation may be lessened

Inversion mutations occur when a section of a gene is cut then resealed after 180° inversion

Duplication of a gene

• A whole gene or section of a gene is duplicated so that two copies of the gene/section appear on the same chromosome
• The original version of the gene remains intact and therefore the mutation is not harmful
• Overtime, the second copy can undergo mutations which enable it to develop new functions
• Duplication mutations are an important source of evolutionary change
  • Alpha, beta and gamma haemoglobin genes evolved due to duplication mutations

Duplication mutations occur when a gene is copied so that two versions of the same gene occur on the same chromosome

Translocation of a gene section

• Similarly to inversion, a gene is cut in two places
• The section of the gene that is cut off attaches to a separate gene
• The result is the cut gene is now non-functional due to having a section missing and the gene that has gained the translocated section is likely to also be non-functional
• If a section of a proto-oncogene is translocated onto a gene controlling cell division, it could boost expression and lead to tumours
• Similarly, if a section of a tumour suppressor gene is translocated and the result is a faulty tumour suppressor gene, this could lead to the cell continuing replication when it contains faulty DNA

Translocation mutations occur when a section of a gene is cut then resealed onto another gene