GENE MUTATIONS (aka point mutations)

Gene mutations are changes in the structure of the DNA which affect only one gene.

Normal gene

The antisense strand is the DNA strand which acts as the template for mRNA transcription.

Mutations

Substitutions

Substitutions will only affect a single codon. Their effects may not be serious unless they affect an amino acid that is essential for the structure and function of the finished protein molecule (e.g. sickle cell anaemia).

Because the genetic code is degenerate it is possible for a mutation to have no effect on the phenotype. Changes in the third base of a codon often have no effect:

Some substitution mutations can, however, be disastrous:

Inversion

Inversion mutations, like substitutions, only affect a small part of the gene:

Addition

Because the genetic code has no “punctuation” the reading frame is set at the beginning of the gene. One additional base will change the whole reading frame from that point on.

Deletion

Removing a base from the gene has a similar effect to addition. It changes the reading frame downstream of the mutation.

Mutations of haemoglobin

Haemoglobin is a tetromer (it has 4 polypeptide subunits – 2 alpha and 2 beta chains). The genes for these polypeptides are found on different chromosomes. The beta chain gene is found on the short arm of chromosome 11. The alpha chain gene is found on chromosome 16. The nucleotide sequences have been worked out. Several inherited diseases occur on the beta chain, which contains 146 amino acids:

The sense strand (coding strand) cDNA sequence of for beta haemoglobin

cDNA (complementary DNA) is obtained by back-transcribing the mRNA used to translate the polypeptide. So cDNA has no introns. This is done using reverse transcriptase enzyme. Here the sequence of only one strand of the cDNA is shown, this is the side which is equivalent to the mRNA strand called the sense or coding strand. The sequence reads from left to right and line by line. It has been divided up into triplets of bases corresponding to the codons. Normally it would be a continuous series of bases.

© Paul Billiet 2008