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 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.

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 a Mutated DNA g a One strand is nicked a DNA removed between nicks a t 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 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

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 number height