What goes wrong with DNA?
- A mistake in translation can produce mRNA with one or more incorrect codons
- Error in cystic fibrosis sufferers is in the DNA as the problems are in every epithelial cell
- Mistakes arise when DNA copies itself curing the process of DNA replication
DNA replication:
- When a cell divides an exact copy of the DNA must be produced so that each daughter cell receives a copy – replication
- DNA double helix unwinds from one end, the two strands split apart as the hydrogen bonds between bases break
- Free DNA nucleotides line up alongside each DNA strand and hydrogen bonds form between the complimentary bases
- The enzyme DNA polymerase links the adjacent nucleotides to form a complimentary strand
- Each strand of DNA acts as a template on which a new strand is built; two complete DNA molecules are formed
- Each of the two new DNA molecules contains one old strand and one new strand – semi-conservative replication
Semi-conservative replication:
- Meselson and Stahl did experiments to show how DNA replicated
- Three possible ways to replicate; fragmentary, conservative, semi-conservative
- Uses light and heavy strands of DNA; achieved by using bacteria that had been grown in a medium containing only the heavy isotope nitrogen, 15
- All the nucleotides in bacteria started out with heavy nitrogen, making the DNA denser than usual (yellow strand)
- Then moved bacteria to a medium containing only normal 14N, meaning all new nucleotides introduced into the replicated DNA were light
- Original; heavy / new; light
- Bacteria was allowed to divide and replicated before being extracted and centrifuged
- When centrifuged the heavy DNA sinks to the bottom while light DNA collects near the top, medium in the middle
- The result: one medium band density (no heavy density left – excluding the conservative model)
- After the DNA was extracted and centrifuged after two rounds of replication gave two bands (one medium, and one light)
- Confirmed semi-conservative model and ruled out fragmentary (that would only be light and heavy)
Mistakes in replication:
- As the new strand is being built an incorrect base may slip into place – mutation
- Sometimes mutations occur in the DNA of an ovary or testis cell that is dividing to form an egg or sperm. This may be passed onto future generations
- Some mutations have no effect
- Genetic disorder; mutation within the gene, and a new base triplet is created that codes for a stop or different amino acid
Sickle Cell Anaemia:
- Mutation in the gene that codes for one of the polypeptide chains in haemoglobin (the pigment in red blood cells which carries oxygen around the body)
- Adenine replaces thymine along the chain
- Protein produced contains the non-polar amino acid valine rather than polar glutamic acid
- Haemoglobin made less soluble
- Distorted shape; oxygen levels are low, molecules form long fibres that stick together inside the cell
- The sickle shaped cells carry less oxygen and can block blood vessels
Mutations and Cystic Fibrosis:
- Hundreds of mutations; affect the CFTR protein in different ways
- Sometimes ATP is unable to bind and open the ion channel
- In other cases the channel is open but changes in the protein structure lead to reduced movement in chloride ions through the channel
- Most common mutation; deletion of three nucleotides (loss of phenylalanine – causing misfolding of protein)
