Overview of the gene
A gene is a sequence of nucleotide pairs that determines the production of a specific product.
Expression of a protein coding DNA requires transcription into mRNA and then translation to form the polypeptide product.
Eukaryotic genes are interrupted by non-coding regions called introns. These are removed by splicing to leave just the coding exons. A 5' cap and a 3' polyA tail are added to form mature RNA.
The genetic code:
- is triplet consisting of 64 3 letter codons
- is degnerate, more than one code can specify an amino acid
- contains an initiation codon (AUG) and three stop codons (UAA, UAG, UGA)
- is universal
Mutations changing the amino acid sequence
The phenotype is the visible symptoms or traits shown in an individual.
In sickle cell disease a single base substituion causes an amino acid substitution from glutamate (Glu) to valine (Val). The changes the structure of haemoglobin and reduces its ability to carry oxygen.
Following generalisations are possible:
- a specific codon can be mutated to give more than one variant
- all nucleotide pairs can mutate with equal frequency
- the severity of the mutatnt phenotype depends on the amino acid change
Mutations affecting the amount of gene product
Mutations can affect the amount synthesised by:
- altering promoter activity (transcription effiiency)
- altering the initiation codon (transcription efficiency)
- preventing splicing (mRNA maturation)
- changing the sequence of the upstream and downstream regions (reducing the stability of the mRNA)
Mutations changing polypeptide length
Mutations that eliminate codon(s) from the gene are called deletions.
An insertion is the reciprocal of a deletion.
A chain-termination mutation gives an abnormally short polypeptide (base substitution creates a stop codon).
Frameshift mutation adds or removes a single nucleotide pair from the gene so the downstream portion is translated "out-of-frame". Polypeptides are normally abnormally long or abnormally short.
Chromosome structural changes
A chromosomal rearrangement is a mutation that alters the position of a large number of nucleoides or genes. They can be:
- deletions: loss of a DNA segment from the chromosome
- inversions: the order of a block of genes is reversed
- translocations: parts of different chromosomes are interchanged
Insertion of a transposable element
Transposable elements are specific DNA sequences that can move spontaneously from one location in the DNA to insert randomly elsewhere.
They may contain genes that are unrelated to movement and are of adaptive value to the cell e.g antibiotic resistance in bacteria.
They are frequently mutagenic as they can insert in the middle of genes causing them to be inactivated.