Gene Mutations (OCR 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
  • Mutations can occur spontaneously (i.e. for no reason) during DNA replication
  • The probability of a mutation occurring can increase with the presence of certain factors known as mutagens, e.g.
    • Ionising radiation such as X-rays can break the DNA strands which can then be altered during the repair process
    • Deaminating chemicals can alter the chemical structure of bases, converting one base into another
    • Methyl or ethyl groups can be added to bases, leading to incorrect base pairing
    • Viruses can insert sections of viral DNA into the DNA of cells
• These mutations usually have no effect on us:
  • As 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 i.e. several different triplets often code for the same amino acid)
  • Many mutations occur in non-coding sections of DNA and so have no effect on the amino acid sequence at all

• However, a mutation in a gene can sometimes lead to a change in the polypeptide that the gene codes for (as the DNA base sequence determines the sequence of amino acids that make up a protein)
• There are three main ways that a mutation in the DNA base sequence can occur:
  • Insertion of one or more nucleotides
  • Deletion of one or more nucleotides
  • Substitution of one or more nucleotides

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
  • Remember – 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
• 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
• Like an insertion mutation, 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
• Unlike an insertion or deletion mutation, a substitution mutation will only change the amino acid for the triplet (a 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

 The effect of gene mutations on polypeptides 

• Based on the effect they have on an organism, gene mutations can be placed into one of three categories:
  • Beneficial mutations
  • Harmful mutations
  • Neutral mutations

Beneficial mutations

• A small number of mutations result in a significantly altered polypeptide with a different shape
• This may alter the ability of the protein to perform its function. For example:
  • If the shape of the active site on an enzyme changes, the substrate may no longer be able to bind to the active site
  • A structural protein (like collagen) may lose its strength if its shape changes

• In some cases, this alteration to a polypeptide may actually result in an altered characteristic in an organism that causes beneficial effects for the organism
  • In these cases, the original mutation is referred to as a beneficial mutation

• An example of a beneficial mutation that occurred in humans involves the production of the pigment melanin:
  • Early humans living in Africa had dark skin as they produced high concentrations of the pigment melanin
  • This provided protection from harmful UV radiation from the Sun, whilst still allowing vitamin D to be synthesised (due to the high sunlight intensity)
  • However, at lower sunlight intensities, pale skin synthesises vitamin D more easily than dark skin
  • As humans moved into cooler temperate climates, certain mutations occurred that led to a decrease in the production of melanin
  • These paler-skinned individuals would have had a selective advantage, as they could synthesis more vitamin D (a lack of vitamin D causes a range of health problems, including rickets and reduced protection against heart disease and cancers)
  • The mutations that led to a decrease in the production of melanin are therefore referred to as beneficial mutations

Harmful mutations

• By altering a polypeptide, some mutations can lead to an altered characteristic in an organism that causes harmful effects for the organism
  • In these cases, the original mutation is referred to as a harmful mutation

• Many genetic diseases are caused by these harmful mutations (e.g. haemophilia and sickle cell anaemia)
• An example of a harmful mutation that occurs in humans is that which causes cystic fibrosis:
  • In around 70% of cystic fibrosis sufferers, the mutation that causes this disease is a deletion mutation of three nucleotides in the gene coding for the protein CFTR
  • The loss of function of the CFTR protein caused by this deletion mutation results in a number of symptoms, including lung and pancreatic problems as a result of extremely thickened mucus

Neutral mutations

• Neutral mutations offer no selective advantage or disadvantage to the individual organism
• This can occur either because:
  • A mutation does not alter the polypeptide
  • A mutation only alters the polypeptide slightly so that its structure or function is not changed
  • A mutation alters the structure or function of the polypeptide but the resulting difference in the characteristic of the organism provides no particular advantage or disadvantage to the organism

• An example of a neutral mutation that occurs in humans involves the ability to taste a bitter-tasting chemical that is found in Brussel sprouts:
  • This chemical is not toxic so it is not advantageous for us to be able to taste it
  • The ability to taste this chemical is caused by a mutated allele of the TAS2R38 gene
  • The TAS2R38 gene allows us to taste bitter things by coding for receptor proteins that can detect bitter-tasting chemicals
  • However, the mutated allele of this gene causes an increased perception of bitterness, meaning that people with this mutation can taste the bitter-tasting chemical in Brussel sprouts (whereas people without the mutation cannot)
  • Although this is now seen as a neutral mutation, it may have been advantageous in the past for humans to be able to detect these bitter-tasting chemicals, as large quantities of bitter substances can be harmful and many poisons have a bitter taste