Enlighten Biology Note on Mutations and Its Effects on Organisms


Gene mutations (when DNA goes wrong)

A mutation is a change in the sequence of bases in DNA.

Protein synthesis can be disrupted if the mutation occurs within a gene.

The change in sequence is caused by the substitution, deletion, or insertion of one or more nucleotides (or base pairs) within a gene.

If only one nucleotide is affected it is called a point mutation.

The substitution of a single nucleotide changes the codon in which it occurs.

If the new codon codes for a different amino acid this will lead to a change in the primary structure of the protein.

The degenerate nature of the genetic code may mean however that the new codon still codes for the same amino acid leading to no change in the protein synthesised.

The position and involvement of the amino acid in R-group interactions within the protein will determine the impact of the new amino acid on the function of the protein.

For example, if the protein is an enzyme and the amino acid plays an important role within the active site, then the protein may no longer act as a biological catalyst.

The insertion or deletion of a nucleotide, or nucleotides, leads to a frameshift mutation.

The triplet code means that sequences of bases are transcribed (or read) consecutively in non-overlapping groups of three.

This is the reading frame of a sequence of bases.

Each group of three bases corresponds to one amino acid.

The addition or deletion of a nucleotide moves, or shifts, the reading frame of the sequence of bases.

This will change every successive codon from the point of mutation.

The same effect is seen however many nucleotides are added or deleted, unless the number of nucleotides changed is a multiple of three.

Multiples of three correspond to full codons and therefore the reading frame will not be changed but the protein formed will still be affected as a new amino acid is added.

Causes of mutations

Mutations can occur spontaneously, often during DNA replication, but the rate of mutation is increased by mutagens.

A mutagen is a chemical physical or biological agent which causes mutations.

The loss of a purine base (depurination) or a pyrimidine base (depyrimidination) often occurs spontaneously.

The absence of a base can lead to the insertion of an incorrect base through complementary base pairing during DNA replication.

Free radicals, which are oxidising agents, can affect the structures of nucleotides and also disrupt base pairing during DNA replication.

Antioxidants, such as vitamins A, C, and E (found in fruit and vegetables), are known anticarcinogens because of their ability to negate the effects of free radicals.

Effects of different mutations

  • No effect – there is no effect on the phenotype of an organism because normally functioning proteins are still synthesised.
  • Damaging – the phenotype of an organism is affected negatively because proteins are no longer synthesised or proteins synthesised are non-functional. This can interfere with one, or more, essential processes.
  • Beneficial – very rarely a protein synthesised results in a new and useful characteristic in the phenotype. For example, a mutation in a protein present in the cell surface membranes of human cells means that the human immunodeficiency virus (HIV) cannot bind and enter these cells. People with this mutation are immune to infection from HIV.

The ability to digest lactose, the sugar present in milk, is thought to be the result of a relatively recent mutation.

The majority of mammals in the world become lactose intolerant after they cease to suckle.

The ability to digest lactose is found primarily in European populations who are more likely to farm cattle.

The ability to drink milk and process lactose as an adult helps prevent diseases such as osteoporosis this could also have prevented individuals with the mutation from starving during famines.

This mutation appears to have arisen spontaneously more than once it has also been found in people in East Africa.

Silent mutations

The vast majority of mutations are silent (or neutral) which means they do not change any proteins or the activity of any proteins synthesised.

Therefore, they do not affect the phenotype of an organism.

They can occur in the non-coding regions of DNA (introns) or code for the same amino acid due to the degenerate nature of the genetic code.

They may also result in changes to the primary structure but do not change the overall structure or function of the proteins synthesised.

Nonsense mutations

Nonsense mutations result in a codon becoming a stop codon instead of coding for an amino acid.

The result is a shortened protein being synthesised which is normally non-functional.

These mutations normally have harmful effects on phenotypes.

Missense mutations

Missense mutations result in the incorporation of an incorrect amino acid (or amino acids) into the primary structure when the protein is synthesised.

The result depends on the role the amino acid plays in the structure and therefore function of the protein synthesised.

The mutation could be silent, beneficial, or harmful.

A conservative mutation occurs when the amino acid change leads to an amino acid being coded for which has similar properties to the original, this means the effect of the mutation is less severe.

In contrast, a non-conservative mutation is when the new amino acid coded for has different properties to the original, this is more likely to affect protein structure and may cause disease.

Chromosome mutations

Gene mutations occur in single genes or sections of DNA whereas chromosome mutations affect the whole chromosome or number of chromosomes within a cell.

They can also be caused by mutagens and normally occur during meiosis.

As with gene mutations, the mutations can be silent but often lead to developmental difficulties.

Changes in chromosome structure include:

  • Deletion – a section of chromosome breaks off and is lost within the cell.
  • Duplication – sections get duplicated on a chromosome.
  • Translocation – a section of one chromosome breaks out and joins another non-homologous chromosome.
  • Inversion – a section of chromosome breaks off, is reversed, and then joins back onto the chromosome.

Sickle-cell anaemia and mutation

The Molecular Basis of Sickle-Cell Disease

Sickle-cell anaemia is a blood disorder where erythrocytes develop abnormally.

The disorder is caused by a mutation in the gene coding for haemoglobin.

There is a substitution of just one base.

Thymine replaces adenine, making the sixth amino acid valine instead of glutamic acid on the beta-haemoglobin chain.

Glutamic acid is a hydrophilic amino acid but valine is a hydrophobic amino acid.

When the partial pressure of oxygen is low, and haemoglobin is dissociated from oxygen, the hydrophobic valine amino acids bind to hydrophobic regions on adjacent haemoglobin molecules.

The aggregation of haemoglobin molecules deforms the shape of erythrocytes causing them to become sickle-shaped.

The erythrocytes are less flexible and have difficulty moving through capillaries resulting in reduced oxygen delivery to tissues, which causes anaemia.

In homozygous individuals, there are two copies of the mutant alleles present.

Heterozygous individuals only get mild symptoms of the condition, but are resistant to malaria.

Hundreds of millions of people get malaria each year with over a million fatal cases.


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