Mutations - in depth

A mutation is change in the amount of or arrangement of the genetic material in the cell. They can be chromosomal mutations which involves changes to parts or whole chromosomes. Or, they can be DNA mutations which are changes to the nucleotide base sequences.

What causes mutations?

• During the process of replication, DNA is normally copied exactly so that the genetic material remains the same from generation to generation. However, occasionally changes can occur so that an organism may inherit altered DNA.
• The sudden change that can occur may produce an individual which is obviously different from the rest of the population. e.g. bacteria resistant to penicillin.
• Altered DNA molecules replicates the changed sequences so that the mutant genes are passed on to successive generations. - Such inherited changes are known as mutations.
• Mutation is another source of genetic variability n a population and it can occur spontaneously. 
• Mutant genes tend to be recessive but are transmitted in the normal way
• most mutations are harmful to the organism but some can be useful
• spontaneous mutations are essential for providing a new variation necessary for survival in a changing environment; in other words, it proves raw materials for evolutionary change
• The frequency with which one allele mutates to another is known as the mutation rate or mutation frequency and is measured by their occurrence in a population 
• mutations tend to be rare but the mutation rate can be speeded up by certain factors called mutagens or mutagentic agents which include x-rays, gamma rays and UV light which can damage DNA in various ways
• mutagens also include certain chemical substances which alter DNA by adding or deleting one or more bases in a sequences
• chemical mutagens include nitrous acid and 5-bromouracil

DNA mutations

• during protein synthesis, the sequence of ases in DNA is transcribed into a complementary sequence of bases in RNA which is then translated into a sequence of amino acids
• each sequence of three bases is a code for a specific amino acid, so that if the code is altered, this may result in an incorrect sequence of amino acids
• these changes would therefore result in non-functional proteins or proteins with a different function

Types of DNA mutations

• Point mutations - one base replaces another - also called substitutions
• Insertion/deletion mutations - one or more nucleotide pairs are inserted/deleted from a  length of DNA which causes frameshift
• A gene mutation in which a nucleotide is left out is called a deletion and a mutation in which a nucleotide is gained is called an insertion. 

• The effect on the sequence of amino acids from this small change in the DNA base is great.
• Every amino acid after the change ight be replaced by a different amino acid.
• both base deletion and base insertion have resulted in a shift so that all subsequent codons are altered.
• it is not surprising that mutation can result in the synthesis of a totally different protein

SICKLE CELL ANAEMIA

• The kind of point mutation that causes sickle cell anaemia is called substitution
• this is because the mutation is due to the substitution of one base for another just one place in the DNA molecule (thymine is replaced by adenine)
• the result of this is that the beta-chains of haemoglobin contains the amino acid valine at position 6 instead of glutamic acid
• Effect
• the haemoglobin is less soluble than normal haemoflobin and causes the RBC to become distorted into a sickle shape.
• this has many effects including severe anaemia and a clumping of cells which may lead to heart failure
• sickle-cell anaemia is often fatal before middle age

CYSTIC FIBROSIS

• 70% of the cases if cystic fibrosis the mutation is the deletion of a triplet base pair
• this deletes one amino acid out of a chain of 1480 in the normal polypeptide
• cystic fibrosis produces extra thick and very sticky mucus
• this can accumulate in the lungs and pathogens would normally be removed in the mucus by cilia  but the cilia are unable to move the mucus and thus causing infection - physiotherapy is required to get rid of it

ONCOGENES

• growth- promoting genes called protooncogenes
• these can be changed to oncogenes by point mutation so they cannot be turned off
• oncogenes promote unregulated cell division so this can lead to tumour. 

HUNTINGTON DISEASE

• Huntington disease results from an expanded triple nucleotide repeat
• the normal gene has a repeating CAG sequence above a certain threshold the protein alters sufficiently to cause the disease
• the symptoms are see later in life and include dementia and loss of motor control

Mutations w/ a neutral effect

• A change in the base sequence may produce no change in the organism if
• the mutation is a non-coding region of the DNA
• is a silent mutation - the change in the base does not alter the amino acid sequence
• the change in the organism is not seen as an advantage or disadvantage e.g. taste

Harmful/Beneficial effects:

• Early humans in Africa almost certainly had dark skin
• the pigment melanin protected them from the UV light
• they could however, still synthesise vit D from the action of intense sunlight on their skin
• humans with mutations resulting in paler skin would have been burned or suffered skin caner
• as humans migrated to more temperate areas sunlight was not intense enough to produce sufficient vit D by those with dark skins
• those with the pale mutations would have had an advantage (as a lack of vit D leads t rickets, narrow pelvis etc.)
• the Inuit peoples have not lost all their skin pigments although they dont live in an area with intense sunlight
• however, they eat a lot of vit D rich fish and seal meat.