The main properties of DNA

1. 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

2. 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…….

3. 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

4. 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

5. 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 its own mistakes (99%). After DNA replication there is a “mismatch repair” system to correct remaining mistakes (99.9%). This leaves an overall error rate of about 1 base in 1010.

6. 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

7. a g a g a a t DNA excision repair • Another system to repair mutated or damaged DNA Mutated DNA One strand is nicked DNA removed between nicks Correct DNA is synthesised

8. 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…..

9. The Ames Test Culture of His- bacteria Petri dishes containing chemical to test, liver extract, no histidine The more mutagenic the chemical, the more His+ colonies are produced Number of colonies Amount chemical

10. 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

11. 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.

12. 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 number height