Put the pictures in the right order B

Put the pictures in the right order! B A C D They are the stages of protein folding – D, C, A, B

Control, Genomes and Environment Cellular Control – Mutations

Starter – Code breaker – what’s happened to the original message? • THE RED HEN ATE THE EGG • THE RED MEN ATE THE EGG • THE RED HEN ATE THE EG • HER EDH ENA TET HEE GG • Mark homework - answers

Learning Outcomes • state that mutations cause changes to the sequence of nucleotides in DNA molecules; • explain how mutations can have beneficial, neutral or harmful effects on the way a protein functions

Definitions Increased by chemicals or radiation sponta dom n a r neous rare – Mutation • A change in gene or chromosome structure – Mutant • An individual showing or carrying a mutation – Mutagen • A chemical or physical agents causing a mutation (UV light, chemicals eg Benzene) • Types of mutations: – Gene mutation • Affects a single gene – results from change in base sequence – A chromosome mutation • Affects a single chromosome or set of chromosomes – removal/addition of parts

Chromosome mutations • An entire chromosome is lost or repeated during cell division. • Example: Downs syndrome is caused by having an extra chromosome 21. • A part of a chromosome is translocated to another or lost entirely. • Example: • Philadelphia chromosome associated with CML

Types of Gene Mutations 99% of mutations have no phenotypic effect on the organism! Substitution – swapping one base for another. Can have no effect because DNA code is degenerate ATG CCT →ATT CCT Deletion – Loss of one base pair. Causes a frame shift, so all the following base triplets are disrupted. ATG CCT →ATC CT Insertion – The addition of a new pair of bases. Also causes a ATG CCT →ATG ACC T frame shift. Duplication – one or more bases repeated. ATG CCT →ATG CCC CT Inversion – a sequence of bases is reversed. ATG CCT →ATG TCC Germline mutations – Mutation in gamete, so can cause genetic diseases and are passed on. Somatic mutations – Not inherited but can cause ageing and cancer. They are as a result of mutations in normal diploid cells.

Mutation Activity • Visualising the effects of mutations

Beneficial Mutations Antibiotic resistance Rats and Warfarin • These are mutation which offer a selective advantage to an individual. – Well-adapted organisms can out-compete those in the population without the advantageous characteristic – This is the driving force behind natural selection – Rare events, but of paramount importance in the evolutionary process • The environment plays a role in determining the likelihood of this characteristic being maintained through natural selection.

Neutral Mutations • Can result in other alleles of the gene • No effect if – – in a non-coding region of the DNA (intron) – A silent mutation • Examples: – Ability to smell honeysuckle flowers – Tongue rolling – Attached earlobes • No advantage or disadvantage to these characteristics – so neutral.

Harmful Mutations - most harmful mutations have been removed from populations over millions of years of evolution. • Cystic fibrosis - the mutation is a deletion of a triplet of base pairs (70% of cases) • Proto-oncogenes can be changed into oncogenes by a point mutation. These can promote uncontrolled cell division • Huntington disease is caused by a ‘stutter’ – this is repeating sections of CAG sequences • Sickle cell anaemia – Result of a mutation in the gene coding for the β chain of haemoglobin (link to AS)

Plenary – What type of mutation is shown in each example? • THE RED HEN ATE THE EGG • THE RED MEN ATE THE EGG • THE RED HEN ATE THE EG • HER EDH ENA TET HEE GG Which is the most harmful and why?

In groups – study a disease resulting from mutation • You will present the key facts to the others in the class via an information card that you will prepare. What mutation type is it? • Cystic Fibrosis Which gene is affected? • Sickle Cell Anaemia What are the effects of the mutation? • • Haemophilia Duchenne Muscular Dystrophy Phenylketonuria Breast Cancer

Sickle Cell Anaemia • Haemoglobin – Globular protein • Two α polypeptide chains • Two β polypeptide chains – A mutation in the gene coding for the β chain causes sickle cell anaemia

Sickle Cell Anaemia

Sickle Cell Anaemia Important to remember to discuss the effect of the code change on the protein! • When the four polypeptide chains curl up they form a specific 3 -D shape – Some amino acids have hydrophobic side chains e. g. valine – Some amino acids have hydrophillic side chains e. g. Glutamate • If the O 2 level in blood falls, valines form bonds with themselves that stick haemoglobin molecules together, producing long chains of stuck-together haemoglobin molecules, the RBC is pulled out of its usual biconcave shape.

Mutation Exam Question • The diagram represents part of the primary and tertiary structure of the newly-discovered enzyme, including its active site. The amino acids are represented by circles, which are numbered to show their position in the primary structure. A research team wanted to change the structure of the enzyme so that (shaded amino acids) form the active site ; it would The function at higher substrate may notaattach to the active site ; temperatures. They used enzyme-substrate complex may not be formed / AW ; technique called site directed mutagenesis. In this technique single changes to the amino acid sequence of the enzyme are planned Suggest why it would be important that this procedure did not change any of the amino acids shaded grey. (1 mark)

Homework • Inherited Metabolic disorders sheet • Q p 109, 111 PB • Q p 108 GB