The main properties of DNA

• The genetic material must be able to:– Store information– Replicate (when cells divide)– Express information (as proteins)– Mutate at a low frequency (less than 1 in a

million)

• DNA is a molecule that is very well suited to doing all 4 of these

Mutation• Can occur in any cell at any time, cause may be:

– Internal (e.g. mistakes during replication of DNA)

– External (e.g. radiation, chemicals)

• Most mutations have no effect (neutral)

• A few mutations are harmful

• A very few mutations are beneficial

• Only harmful and beneficial mutations are acted on by natural selection

• Mutations may be non-coding (not in part of gene that codes for protein - have no effect, or affect gene expression) or coding…….

Effects of coding mutations

• Synonymous: the cat ate the rat

• Missense: the fat ate the rat

• Nonsense: the cat ate the

• Frameshift: the cax tat eth era t

• Synonymous has no effect on protein, nonsense makes a smaller protein, missense/frameshift make incorrect protein

Conditional mutations• The effects of many coding

mutations depend on environmental factors

• Siamese cats have mutation in enzyme for black pigment production, that stops it working at normal body temperature

• Cooler parts of cat are dark because enzyme OK at lower temperature

Mutation during DNA replication

• Replication of DNA is not perfectly accurate, but there are several ways to correct the mistakes

ACGTACGTAACGTG...TGCATGCATTGAACGGT

DNA polymerase makes about 1 mistake per 105 bp.DNA polymerase has a “proof-reading” activity to correct itsown mistakes (99%).After DNA replication there is a “mismatch repair” system tocorrect remaining mistakes (99.9%).This leaves an overall error rate of about 1 base in 1010.

Mutation due to environmental factors

• Mutations may be caused by chemicals or radiation

• Chemicals (“mutagens”) may disrupt hydrogen bonds between bases, by modifying them or getting between them

• Radiation (including ultra-violet and radioactive emissions) can damage structure of bases

• These agents may be natural or man-made

DNA excision repair

• Another system to repair mutated or damaged DNA

ag

ga

a

at

Mutated DNA

One strand is nicked

DNA removed between nicks

Correct DNA is synthesised

Application - mutagen testing

• Mutation in somatic (body) cells during the lifetime of an animal can cause cancer

• It is vital to know if chemicals to which we are exposed are mutagenic

• Bacteria can be used to test this: the Ames Test

• Reverse mutation is where the mutant form of an organism mutates again, to go back to the original wild-type state

• The Ames Test uses a mutant strain of bacterium Salmonella typhimurium that cannot make the amino-acid histidine…..

The Ames Test

Culture ofHis- bacteria

Petri dishes containing chemical to test,liver extract, no histidine

Amount chemicalNum

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The more mutagenic the chemical,the more His+ colonies are produced

Phenotype, Genotype, Alleles• The phenotype of an organism is its observable

properties• The genotype is the set of alleles it has for all of

its genes (5,000 in bacteria; 40,000 in humans)• The relationship between genotype and phenotype

is what genetics is all about• New alleles are created by mutation and their

effect the phenotype may be dominant or recessive

Significance of genetic variation• Some alleles directly cause specific traits, such as

(in humans) rare genetic diseases e.g. Cystic fibrosis, sickle-cell anaemia; (in bacteria) ability to grow on certain sugars

• Many alleles contribute to many traits of an organism such as size, shape, intelligence, behaviour, and risk of getting diseases e.g. (in humans) cancer, heart disease, asthma

• Genetic variation is what evolution acts on. Without it there would be no different species.

Multiple genes and quantitative traits

• Many traits like height, IQ show a bell-shaped (normal) distribution in population

• These are influenced by several genes, so the overall effect depends on the random selection of alleles in an individual

• e.g. for height genes, you are more likely to have a mixture of tall and short alleles than all tall or all short

height

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