Consequences of Gene Mutations (HL IB Biology)

• Base substitutions are a mutation that occurs when a base in the DNA sequence is randomly swapped for a different base
  • A substitution mutation can only change the amino acid for the triplet in which the mutation occurs; it will not have a knock-on effect on the rest of the sequence
• A base substitution can result in single nucleotide polymorphisms, frequently called SNPs (pronounced “snips”)
  • These represent a difference in a single DNA  nucleotide. E.g. a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA
• SNPs occur normally throughout a person’s DNA
  • They occur once in every 300 nucleotides on average, which means there are roughly 10 million SNPs in the human genome
• SNPs are commonly found in the non-coding regions of DNA between genes
• They can act as biological markers, helping to locate genes that are associated with disease

The effect of SNPs

• Substitution mutations can take three forms which may or may not change the amino acid of a polypeptide chain:
  • 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)

• Insertions and deletions are two types of point mutations, which are mutations that involve a change in the DNA base sequence at a single location
  • An insertion occurs when an extra nucleotide is incorporated into the DNA sequence during replication
  • A deletion mutation occurs when a nucleotide is missed or absent from the replicated strand
• These mutations are often considered more harmful than substitutions, because they impact on the way the rest of the sequence is read by mRNA or the ribosome
• Insertions and deletions of nucleotides can also have the effect of a frameshift mutation
• This causes a complete change to the entire amino acid sequence of a protein after the mutation site and can cause the polypeptide to cease to function
• This happens because of the way the translated mRNA is read by the ribosomes
  • The mRNA is read in codons (groups of 3 nucleotides) so if an additional 1 or 2 nucleotides are added or removed, the sequence is ‘shifted’
  • The ribosome still reads the sequence of  triplet codons along the length of mRNA which means the entire mRNA and resulting protein are completely different
• The result of frameshift mutation means the entire DNA sequence following the mutation will be incorrectly read. This can result in the addition of the wrong amino acids to the polypeptide chain and/or the creation of a codon that stops the protein from growing longer
• Although a frameshift mutation during translation is rare (10⁻⁵ to 10⁻⁷ per codon), the effects are generally catastrophic for the resulting protein
• The same can be said for large insertions and deletions of nucleotides of the DNA sequence

Consequences of Mutations Diagram

Insertion and deletion mutations can cause a frameshift in the sequence of bases which can drastically alter the amino acid coded for. The resulting protein may be very different to the original intended.

• The effect of a mutation can vary depending on whether it occurs in a germ cell or somatic cell
  • A germ cells use meiosis to produce gametes
  • Somatic cells use mitosis to produce cells all over the body which can grow into tissues and organs

Germ cells

• If a mutation occurs in a germ cell it can be passed on to the offspring and next generation
  • Cells involved in inheritance of genetic information, eggs, sperm and zygote, are know as the germ line
  • A mutation that occurs in sperm cells could potentially affect the zygote of that offspring and all cells developed from that zygote will contain the mutation
  • A female that has inherited a mutation will contain the mutation in the germ cells of their ovaries which will be passed onto future offspring

Somatic cells

• Somatic cell mutations are not inherited by offspring, instead these mutations are associated with cancers
• Cancers demonstrate how important it is that cell division is precisely controlled, as cancers arise due to uncontrolled mitosis
• Cancerous cells divide repeatedly and uncontrollably, forming a tumour (an irregular mass of cells)
• Cancers start when a mutation occurs in the genes that control cell division
• If the mutated gene is one that causes cancer it is referred to as an oncogene
• Mutations are common events and don’t lead to cancer most of the time
  • Most mutations either result in early cell death or result in the cell being destroyed by the body’s immune system
  • As most cells can be easily replaced, these events usually have no harmful effect on the body
• The mutations that result in the generation of cancerous cells do not result in early cell death or in the cell being destroyed by the body’s immune system