Introduction

1. Introduction Mrs Jones • 10 years at The Heathland School, twice into this School for A 'Level revision • My website: Mrs Jones A-Level Biology: mrsjonesbiology.weebly.com • Your page: http://mrsjonesbiology.weebly.com/rivers-academy • I can upload resources, there is also a blog page if you need requests. • What do I expect from you? (notes/questions/pace) • What do you want from me??? • How do you learn best? • SOW Learning outcomes • Starting Topic 6 re feedback from Ms Mohey • Need to sort what you would like to cover next week: • Any questions??

2. List completed in Easter Holidays Kidney  failure Dialysis (including difference between peritoneal and haemodialysis) Cloning techniques Sliding filament model Ecosystem calculations (biomass) Chapter 12 Homeobox genes: today Hardy-Weinberg Speciation DNA Sequencing Making medicine First List from Ms Mohey • Module 6: just starting today..what other bits to do? • Enzyme exam questions • Cell division exam questions • Exchange surfaces / fish • Transport in animals - blood vessels • Transport in plants • Biodiversity equations • Communicable diseases • T and B lymph  • Homeostasis – kidneys • Plant responses • Photosynthesis • Cardiac cycle

3. 6.1 Genetics and evolution 6.1.1 Cellular control (page 506) Use the LO from the spec!!

4. Homework • Revise • DNA structure • DNA replication • Protein synthesis • Protein structure • Mitosis • Meiosis

5. What is the difference?

6. Mutations: Somatic cell mutations/Body cells • Occur in a single body cell and cannot be inherited (only tissues derived from mutated cell are affected) • Not passed on: affect that individual only Germ line mutations: • Mutations in the DNA of the gametes (sperm/egg cell) (every cell in the entire organism will be affected) • Passed on to future generations • Give me a definition for Mutation

7. Mutation A mutation is a change in a base sequence in DNA which can give rise to a change in amino acid sequence in the protein Mutations may occur spontaneously, as a result of errors during Meiosis or DNA replication. In mitosis for somatic (cancer) Or they may be induced: mutagens (increase the natural mutation rate) What are the consequences of a mutation? May cause a new polypeptide to be made and so a new protein. It is unlikely the new protein will function the same.... SYNOPTIC: DNA STRUCTURE/DNA REPLICATION and PROTEIN STRUCTURE/MEIOSIS

8. SYNOPTIC: DNA STRUCTURE and DNA REPLICATION : 10 minutesIn pairs under 2 separate titles give me a list of key words to summarise these 2 topics DNA REPLICATION Semi conservative replication DNA unwinds Hydrogen bonds broken by enzyme helicase The 2 strands separate Each strand acts as a template for the formation of a new molecule of DNA Activated free nucleotides pair with the newly exposed bases by complementary base pairing DNA polymerase catalyses the formation of the phosphodiester bonds between the new nucleotide strands 2 identical molecules of DNA are formed Each new molecule is composed of one original strand and one newly formed molecule: semi conservative replication DNA STRUCTURE • Nucleic acid • Nucleotides: monomer • Polymers: polynucleotide • Deoxyribose sugar: pentose • Phosphate group • Nitrogenous base: adenine, guanine, cytosine, thymine • Bases are pyrimidines(Thymine,Cytosine) or purines (Adenine,Guanine) • Condensation reactions link monomers • Phosphodiester bonds between carbon 5 on the sugar and the OH group of carbon 3 • Sugar phosphate backbone • Two strands running antiparallel, joined by hydrogen bonds • Twisted into a Double Helix • Complementary base pairing, A+T (2 Hydrogen bonds) ; C+G (3 hydrogen bonds) • Pyrimidine +Purine bases join

9. Anti-parallel Anti-parallel

10. DNA replication Base pair rule applies A with T/C with G NB: each strand acts as the template for the assembly of another complimentary strand i.e. same sequence of bases DNA molecule unwinds Each new molecule consists of one original strand and one new strand This is called semi-conservative replication

11. Mini plenaryComplete the exam question 8 marks • A DNA molecule consists of two strands of mononucleotides. Each of theses strands is twisted around the other, forming a ------------ -----------------. • Each mononucleotide consists of a pentose sugar called-----------------,a base and a ----------------------. • In each strand the mononucleotides are held together by------------------ bonds • The 2 strands are held together by complimentary base pairing. Adenine bonds with -------------, and cytosine bonds with -----------------------. • The name of the bond that forms between these bases is a ----------------------- bond • A DNA molecule that is composed of 34% adenine will be composed of ----------------- % cytosine

12. Double helix • Deoxyribose • Phosphate/phosphate group • Phosphodiester/covalent • Thymine • Guanine • Hydrogen • Sixteen/16 (34+34=68; 100-68=32; 32/2=16)

13. Mini plenary 2: 15 minutes • SORT THE STATEMENTS: Complete then discuss in pairs: • 5 minutes • INDIVIDUALLY: Complete exam question: without any support if you can!! • THEN MARK: 10 marks= 10 minutes

14. Deoxyribonucleotide (found in DNA) OH O P OH O Simplified diagram CH2OH O Rest of base molecule C N C H H H H C C Base molecules (Nitrogen containing compound) are Adenine, Thymine, Guanine, Cytosine OH H

15. LO: Lesson 2 • Types of gene mutations and their possible effects on protein production and function • To include substitution, insertion or deletion of one or more nucleotides AND • The possible effects of these gene mutations (i.e. beneficial, neutral or harmful).

16. What are the effects of mutations? • Source of variation, can be advantageous e.g. a superior protein; or neutral or damaging. • Can happen in any cell anytime e.g. Cancer • What are the most damaging mutations? • Those that occur in the gametes • During DNA replication: passed to new cells • Causes a Genetic disorder e.g cystic fibrosis/Downs syndrome

17. GENETIC MUTATIONS:Point mutations: • Gene mutations are small, localised changes in the structure of a DNA strand. They can involve a single nucleotide (point mutations), or can involve changes to a whole triplet. A point mutation is an alteration in the base sequence of 1 base pair/nucleotides, by addition, deletion or substitution • Point mutations occur at a single gene locus on a chromosome, and only one nucleotide is affected, altering the DNA sequence of bases • The DNA bases (triplet code) determine the order of the amino acids in the primary structure of a protein • This can change the final 3D structure of the protein so it does not work properly SYNOPTIC: WHAT CHANGES: THINK PROTEIN STRUCTURE! What are addition/substitution/deletion? In pairs use whiteboards to explain what could happen to this piece of DNA if affected by any of the above point mutations AAAATGCTTCTC Or this statement: the old men saw the lad 10 minutes

18. Types of gene mutation: These only affect one gene Substitution: one or more DNA bases are replaced by another. This changes the triplet code, so the codon could code for a different amino acid, change in primary structure of protein. Sickle cell anaemia is a substitution mutation (no frameshift) Deletion: one or more DNA bases are removed. Cystic fibrosis is caused by a deletion mutation. Addition/ insertion: one or more DNA bases are added. Deletions and additions usually cause a frame shift which causes many amino acids to change. • Triplet code!

19. Examples of Gene Mutations Original sequence - the old men saw the lad Addition- the cold men saw the lad Deletion- the old men saw the ad Substitution- the old hen saw the lad Frame Shift Mutations such as additions and deletions cause the nucleotides after the change to be moved. This means that all subsequent codons are changed. This is a frame shift Other types of mutation include: Inversion - the old men was the lad Duplication- the old old men saw the lad

21. Effect of different mutations on phenotype 1. Silent: No effect/neutral on the phenotype as normally functioning proteins produced. Vast majority of mutations are silent THINK: WHY?HOW? 3 marks The mutation could take place in an intron region; amino acids can be coded for by more than one triplet code (degenerate); the primary structure may change, but it has no impact on the overall structure or the function of the protein produced. 2. Damaging: Phenotype is affected, protein no longer made/ non-functional. 3. Beneficial: Protein produced has new/useful characteristics Examples : see next slide plus we will learn about the sickle cell codominant heterozygous trait as we go through the topic. http://biomedipedia.blogspot.co.uk/2014/09/beneficial-mutations.html

22. Extension/Application????????? • There are 3 types of substitution mutations: Silent, Nonsense and missense • A nonsense mutation • Occurs when one nucleotide is substituted and this leads to the formation of a stop codon instead of a codon that codes for an amino acid. • A stop codon is a certain sequence of bases (TAG, TAA, or TGA in DNA, and UAG, UAA, or UGA in RNA) that stops the production of the amino acid chain. • It is always found at the end of the mRNA sequence when a protein is being produced, but if a substitution causes it to appear in another place, it will prematurely terminate the amino acid sequence and prevent the correct protein from being produced. It will produce a much shorter protein • (EXTENSION/Application link: https://biologydictionary.net/point-mutation/)

23. Missense mutation: • There are 3 types of substitution mutations: Silent, Nonsense and missense • A missense mutation occurs when one nucleotide is substituted and a different codon is formed; but this time, the codon that forms is not a stop codon. Instead, the codon produces a different amino acid in the sequence of amino acids. • For example, if a missense substitution changes a codon from AAG to AGG, the amino acid arginine will be produced instead of lysine. • A missense mutation is considered conservative if the amino acid formed via the mutation has similar properties to the one that was supposed to be formed. The effect is less severe • It is called non-conservative if the amino acid has different properties to the structure and function of a protein.

24. EXTENSION?Application: Morphs “Morphs” In 1946 Nobel Prize winner Hermann J. Muller (1890-1967) coined the terms amorph, hypomorph, hypermorph, antimorph and neomorph to classify mutations based on their behaviour in various genetic situations. Amorphic describes a mutation that causes complete loss of gene function. Amorph is sometimes used interchangeably with "genetic null". An amorphic mutation might cause complete loss of protein function by disrupting translation ("protein null") and/or preventing transcription ("RNA null") These would normally be recessive alleles as they have no function, an amorph is a true genetic and molecular null allele, a complete knockout of the gene, where there is no measurable function left Hypomorph: a mutation that results in reduction of function of a protein. More likely to be recessive alleles as less function than the true protein. Hypermorph: is a mutation that results in the gain of a function of a protein. A Hypermorph would have dominant alleles, as these are now expressed https://ipfs.io/ipfs/QmXoypizjW3WknFiJnKLwHCnL72vedxjQkDDP1mXWo6uco/wiki/Muller's_morphs.html

25. Mini plenary 2 exam questions: 10 minutes= 10 marks

27. Beneficial mutations: example • Ability to digest lactose (sugar in milk) is thought to be the result of a recent mutation • Majority of mammals become lactose intolerant after suckling ceases. • WHY? • Milk provided nutrients that weren't present in the first wave of domesticated crop • Ability to drink milk is advantageous: osteoporosis.

28. Beneficial mutations: example • CCR5-delta 32: HIV Immunity in Humans • A mutation in a protein present in cell surface membranes of human cells means that HIV cannot bind and enter these cells. People are immune to infection from HIV: • DETAIL: • CCR5 is a receptor molecule, located in the membranes of white blood cells (WBCs) and nerve cells. • In a cell, CCR5 permits the entry of chemokines that signals the inflammatory response to any foreign particles. • The gene responsible for coding CCR5 is present in the human chromosome 3. A mutation in this gene called CCR5-delta 32 (involving deletion of 32 base pairs) affects the normal functioning of the CCR5.In the initial stages of HIV infection, the virus normally enters through CCR5. However, a mutated CCR5 blocks the entry of HIV. • People carrying homozygous mutated CCR5-delta 32 are resistant to HIV, while heterozygous ones are beneficial, as they slow down the disease progression. Thus, CCR5-delta 32 provides partial or complete immunity to HIV. Chemokines are tiny protein molecules that form a subfamily of the cell signalling molecules or cytokines. (Interleukins are a group of cytokines (secreted proteins and signal molecules) that were first seen to be expressed by white blood cells) These tiny proteins are secreted by cells to induce chemotaxis in nearby cells. Chemotaxis refers to when cells direct their movement according to the presence of chemicals in their surrounding environment. For example, the presence of a microbe or a foreign body triggers the release of chemicals that then direct immune cells to migrate towards the site of infection. Neutrophils are induced to leave blood vessels and migrate towards the site of infection where the invading body is present.. Chemokines are therefore chemotactic cytokine

29. Damaging mutations • Disadvantageous effect on the organisms survival, the phenotype is affected because a protein is no longer produced or it is non functional Examples: • Cystic fibrosis • Sickle cell anaemia • Mutations can also affect whether or not a protein is produced, mutation could be in the promotor region so RNA polymerase cannot bind.

30. Point mutation Substitution:Sickle cell anaemia • Erythrocytes develop abnormally • Arises because of a substitution mutation in a single codon, in the amino acid sequence of the ß-chain in haemoglobin. • There is a substitution of 1 base, thymine replaces adenine, which makes the 6th amino acid valine instead of glutamic acid • Haemoglobin: less soluble, when oxygen levels are low, the molecules form long fibres that stick together, distorting rbc shape: carries less oxygen/ blocks blood vessels • When is this advantageous?? • Carriers (Heterozygous) of the sickle cell allele are resistant to malaria, because the parasites that cause this disease are killed inside sickle-shaped blood cells. • It is a: Non conservative missense substitution mutation!!!

31. CF mutations • 1:25 people in UK carry the CF gene About 8,000 people in UK have the disease • Over 500 different mutations have been identified • Affect CFTR protein different ways • Most common is the deletion of 3 bases in the gene that codes for the CFTR protein. This folds incorrectly, and leads to excessive mucus production • Genetic mutation: passed to offspring but has to be homozygous recessive

32. MINI PLENARY: Question: 5 marks • Genetic disorders, such as cystic fibrosis, are caused by mutations in the sequence of bases found in DNA. • Explain how a gene mutation may result in a protein that does not function normally 5 marks • TIP: think protein structure/synoptic

33. Definition/description of a gene mutation: A mutation is a change in a base sequence on DNA which can give rise to a change in amino acid sequence in the protein (1) • This causes a change in the mRNA codon. So a different/wrong/no amino acid included due to substitution/ deletion/ inversion/addition (1) • Different sequence of amino acids/primary structure of protein (1) • Different R groups (1) • Change in bonding of protein /correctly named bonds (1) • Protein forms a different secondary/tertiary structure (1) • Different 3D shape (1) • Max 5!

34. Whole Chromosome mutations: • Chromosome mutations affect the whole chromosome/parts of chromosome; they can be caused by mutagens and normally occur during meiosis • Can involve changes to either the number of chromosomes or to large sections of a single chromosome • Whole chromosome lost or duplicated in meiosis • Can be silent. • Deletion: section of chromosome breaks off and is lost • Duplication: sections get duplicated • Translocation: section breaks off and joins another chromosome • Inversion: breaks off, reversed, then joins back on • SYNOPTIC HERE: MEIOSIS • Revise for HW?

35. Example: Down’s syndrome • The number of a particular chromosome is not diploid • It is caused by a mutation in meiosis on chromosome 21 • A pair of homologous chromosomes fail to separate properly so one daughter cell receives both chromosomes and one daughter cell has no chromosomes from that pair. • Affected individuals have 3 copies of chromosome 21

36. DOWN’S SYNDROME Obvious physical features are broad forehead, downward sloping eyes, folds in eyelids, short nose, protruding tongue Mental impairment: range of severity Reduced fertility, heart disease. More common in children of older mothers: • 1 in 2300 children of mothers aged 20 years • 1 in 40 of mothers aged 45+ • Tested!

37. Mutagens: Mutations often occur spontaneously during DNA replication But rate of mutation can be affected by mutagens A mutagen is a chemical, physical or biological agent that causes mutation and increase the rate of mutation

38. Mutagens. these increase the rate of mutation Physical Mutagens: X rays, gamma rays, radiation, UV light can all cause mutation by breaking one or both strands of DNA. Some breaks can be repaired but mutations can occur X-rays and gamma rays can all penetrate deep into the body and cause mutations in any tissue. Damage is especially serious in tissue where cell division is rapid e.g. bone marrow where blood cells are made. The effects of mutagens are cumulative. Chemicals Deaminating agents: Chemicals can chemically change the bases so they pair up wrongly • e.g. nitrous acid converts C  U • In DNA, so changes the base sequence

39. Mutagenic Agents: Biological agents • Viruses: viral DNA can insert itself into a genome • Base analogs: inserted into DNA in place of usual base • (Base analogs are a chemical which resembles a purine or pyrimidine base. Base analog mutagens are chemicals that mimic bases to such an extent that they can be incorporated into DNA in place of one of the normal bases but in doing so lead to an increase in the rate of mutation) • Alkylating agents: methyl/ethyl groups attach to bases, causing incorrect pairing of bases in replication

40. Mini plenary: exam question: 4 marks=4 minutes Meiosis is a source of genetic variation. Mutation is another source of variation. (i) What feature of the DNA molecule is changed as a result of mutation? ...................................................................................................................................... [1] (ii) Discuss the possible effects that mutation can have on the structure and function of a protein. [3]

41. (i) sequence / order, of bases / nucleotides ; 1 CREDIT base pairs DO NOT CREDIT amino acid sequence (ii) different, primary / secondary / tertiary, structure ; (protein ) shorter due to, deletion / stop codon OR longer due to, insertion / duplication ; (protein) unchanged due to, silent mutation / non-coding DNA altered ; (function is) lost / worse / better ; 3 ACCEPT different sequence or order of amino acids ACCEPT different 3D folding or 3D shape for ‘silent’ CREDIT ‘neutral’ or a description of more than one triplet coding for one amino acid IGNORE different / altered function ACCEPT idea that change is harmful

42. Reflect on LO: • Types of gene mutations and their possible effects on protein production and function • To include substitution, insertion or deletion of one or more nucleotides AND • The possible effects of these gene mutations (i.e. beneficial, neutral or harmful). • TASKS: 15 minutes • Define mutation • Explain what occurs in substitution, insertion and deletion mutations • What are the effects of different mutations? • Describe some beneficial mutations • Describe some harmful mutations • What is a chromosome mutation? What changes in chromosome structure can occur?

43. Starter: Use whiteboards • Quick paired reminder of the mechanism of protein synthesis • What are the key words you should be including in your description?? • COMPETITION!! IN PAIRS • How confidant are you???

44. Protein synthesis Gene DNA Triplet code Degenerate Amino acid Polypeptide Sense strand (coding strand) Transcription mRNA Uracil Template strand (antisense strand) Phosphodiester bonds RNA polymerase Hydrogen bonds Complementary Phosphoryl groups (energy) Coding strand Nuclear pore Ribosome Translation Codon Anticodon tRNA AUG=start mRNA Amino acid Peptide bond Stop codon: UAA,UAG,UGA

45. Task • Complete the Protein synthesis summary sheet • EXTENSION: WHAT COULD YOU ADD??? • Add or write your own summary!!

46. LO: Control of gene expression • The regulatory mechanisms that control gene expression at the transcriptional level, post -transcriptional level and post-translational level • To include control at the, • transcriptional level: lac operon, and transcription factors in eukaryotes. • post-transcriptional level: the editing of primary mRNA and the removal of introns to produce mature mRNA. • post-translational level: the activation of proteins by cyclic AMP. • (Synoptic: protein synthesis! REVISE!) • What is the fundamental principle underlying this topic??

47. Gene expression: • All the cells in an organism carry the same genes/entire genome • But structure and function of cells vary. • Not all genes are expressed (transcribed to make functional proteins) and the rate of synthesis of proteins needs to be controlled • Genes control protein synthesis. Some proteins are required all the time by cells whilst others are only needed in specific circumstances and so are not made all the time. • Gene regulation is required for cells to specialise and work in a coordinated way. (saves energy too!) • Gene regulation is similar in Prokaryotes and Eukaryotes, but the stimuli that cause the changes and the responses are more complex in Eukaryotes. So gene expression can be controlled in different ways • Transcriptional: genes turned on/off :DNA structure/lac operon/TF • Post transcriptional: mRNA can be modified • Translational: translation can be stopped/started • Post translational: proteins can be modified after synthesis which changes function/cyclic AMP

48. For a gene to be expressed, two things are necessary: • The DNA must be accessible, not buried in densely packed chromatin=DNA MODIFICATION/EPIGENETICS • Sequence-specific DNA-binding proteins (transcription factors) must bind to the promoter, prior to the sequence to be transcribed, to help recruit RNA polymerase).

49. Modified DNA: • Are we happy with DNA structure?? • In Eukaryotic cells DNA is wound very tightly around histone proteins= chromatin • Chromosomal DNA is packaged inside microscopic nuclei with the help of histones. • These are positively-charged proteins that strongly adhere to negatively-charged DNA and form complexes called nucleosomes. Each nucleosome is composed of DNA wound 1.65 times around eight histone proteins