Topic D DNA Genomics H2 2015

NANYANG JUNIOR COLLEGE H2 Biology DNA and Genomics J1/2015 1 DNA AND GENOMICS Learning Outcomes Core Topic 2 – DNA and Genomics Candidates should be able to (a) Describe the structure and roles of DNA and RNA (tRNA, rRNA and mRNA). (Mitochondrial DNA is not required.) (b) Describe the process of DNA replication and the exp erimental evidence for semi -conservative replication. (c) Describe how the information on DNA is used to synthesize polypeptides in prokaryotes and eukaryotes. (Description of the processes of transcription, formation of mRNA from pre -mRNA and translation is required.) (d) Explain how a change in the sequence of DNA nucleotide (gene mutation) may affect the amino acid sequence in a protein, and hence the phenotype of the organism e.g. sickle cell anaemia and cystic fibrosis. (Knowledge of substitution, addition, de letion and frameshift mutation is required.) Content Outline 1. Introduction 2. Nucleic Acids (a) Structure of nucleotides (b) Structure of polynucleotides (c) Deoxyribonucleic acid (DNA) (d) Ribonucleic acid (RNA) (e) Similarities and differences between DNA and RNA 3. DNA Replication (a) Models of DNA replication (b) Evidence for semi-conservative DNA replication (c) Semi-conservative replication (d) Importance of base-pairing and hydrogen bonding in DNA 4. Gene Expression (a) The Central Dogma of molecular biology (b) Transcription (c) Post-transcriptional modification (d) The Genetic Code (e) Translation (f) Differences between prokaryotic and eukaryotic gene expression 5. Gene Mutation and its Effects (a) Types of gene mutation (b) Effects of gene mutation (c) Sickle Cell Anaemia (d) Cystic fibrosis

NANYANG JUNIOR COLLEGE H2 Biology DNA and Genomics J1/2015 2 References 1. Alberts B., Johnson A., Lewis J., Raff M., Roberts K. and Watts P. (2002) Molecular Biology of the Cell. 4th Edition. Chapter 6: How cells read the genome: From DNA to Protein. Garland Science, Taylor and Francis Group. 2. Campbell N. A. and Reece J. B. (2008). Biology. Chapter 5: T he structure and function of biological molecules. 8th Edition. Benjamin Cummings Publishing, Inc. 3. Campbell N. A. and Reece J. B. (2008). Biology. Chapter 16: The molecular basis of inheritance. 8th Edition. Benjamin Cummings Publishing, Inc. 4. Campbell N. A . and Reece J. B. (2008). Biology. Chapter 17: From gene to protein. 8th Edition. Benjamin Cummings Publishing, Inc. 5. Clegg C. J. and MacKean D. J. (2000). Advanced Biology – Principles and Applications. Chapter 9: The nucleus in division and interphase. 2nd Edition. John Murray Publishers Ltd. 6. Jones M. and Jones G. (2004). Advance Biology. Chapter 5: DNA and protein synthesis. 1 st Edition. Cambridge University Press. 1. Introduction The American James Watson and Englishman Francis Crick solved the puzzle of deoxyribonucleic acid (DNA) structure. Watson saw an X -ray diffraction image of DNA (below, right) revealed by a technique called X-ray crystallography produced by Rosalind Franklin (below, left) and Maurice Wilkins. From the analysis of X-ray diffraction photo of DNA, the structure of DNA molecule:  is a helix made up of two strands.  has a uniform width of 2nm.  is a helix that makes one full turn every 3.4 nm.  has a 0.34nm distance between stacked nitrogenous bases.

NANYANG JUNIOR COLLEGE H2 Biology DNA and Genomics J1/2015 3 In April 1953, Watson and Crick (below, left) surprised the scientific world with a succinct, one - page paper in the British Journal, Nature. The paper reported their molecular model for DNA : the double helix which has since become the symbol of molecular biology. Structure of DNA and RNA

NANYANG JUNIOR COLLEGE H2 Biology DNA and Genomics J1/2015 4 2. Nucleic Acids There are 2 types of nucleic acids:  deoxyribonucleic acid (DNA)  ribonucleic acid (RNA). Nucleotides are the monomers of nucleic acids (polynucleotides).  Deoxyribonucleotides are the monomers of deoxyribonucleic acid (DNA)  Ribonucleotides are the monomers of ribonucleic acid (RNA). (a) Structure of nucleotides A nucleotide consists of 3 components: (i) a pentose sugar, (ii) a nitrogenous base & (iii) one or more phosphate groups (derived from phosphoric acid). The three components are joined by condensation reaction.  The nitrogenous base is bonded to 1’ carbon of the pentose sugar molecule.  The phosphate group is bonded to 5’ carbon of the pentose sugar molecule.  Two molecules of water are formed. Structure of nucleotide and their components

NANYANG JUNIOR COLLEGE H2 Biology DNA and Genomics J1/2015 5 A nucleoside is a molecule consisting of:  a pentose sugar and  a nitrogenous base. E.g. A denosine is a nucleoside with a pentose sugar (ribose) and the nitroge nous base (adenine). A nucleotide is a molecule consisting of:  nucleoside (pentose sugar + nitrogenous base) and  phosphate group(s) E.g. Adenosine monophosphate is a nucleotide. Structure of adenosine Structure of nucleotide (adenosine monophosphate) (i) Pentose Sugar  5-carbon sugar.  2 different types of pentose sugars: ribose and deoxyribose.  In ribonucleic acid (RNA), the pentose sugar is ribose.  Ribose has a hydroxyl group at 2’ carbon.  In deoxyribonucleic acid (DNA), the pentose sugar is deoxyribose.  Deoxyribose has a hydrogen atom at 2’ carbon. Structure of ribose and deoxyribose Ribose Deoxyribose

NANYANG JUNIOR COLLEGE H2 Biology DNA and Genomics J1/2015 6 (ii) Nitrogenous bases  Has one or two ring structures containing nitrogen atoms.  Are known as a “base” due to the presence of lone pair of electrons on nitrogen atoms which tend to accept H+ from solution.  2 categories of nitrogenous bases: purines and pyrimidines.  5 different types of nitrogenous bases: adenine, guanine, cytosine, thymine & uracil.  Purines  2 rings: one 6-membered ring fused to one 5-membered ring  adenine (A) & guanine (G)  Pyrimidines  1 ring: one 6-membered ring  cytosine (C), thymine (T) & uracil (U) o T is only found in DNA o U is only found in RNA Structure of nitrogenous bases

NANYANG JUNIOR COLLEGE H2 Biology DNA and Genomics J1/2015 7 (iii) Phosphate group  Derived from phosphoric acid  attached to 5’ carbon of pentose sugar Structure of phosphoric acid (b) Structure of polynucleotides Many nucleotides joined together to form polynucleotides. They are joined by strong covalent bonds called phosphodiester bonds / linkages. Phosphodiester bonds are formed by condensation reaction between:  –OH group on 3’ carbon of pentose sugar of one nucleotide and  phosphate group on 5’ carbon of pentose sugar of the next nucleotide. Formation of phosphodiester bonds

NANYANG JUNIOR COLLEGE H2 Biology DNA and Genomics J1/2015 8 The resulting structure is a backbone with a repeating patt ern of sugar -phosphate called the sugar-phosphate backbone, with nitrogenous bases projecting out. The two ends of the polynucleotide are different from each other.  5’ end of a polynucleotide has a phosphate group attached to 5’ carbon of sugar.  3’ end of a polynucleotide has a hydroxyl / –OH group on 3’ carbon of sugar. Structure of polynucleotide Nucleoside triphosphate

NANYANG JUNIOR COLLEGE H2 Biology DNA and Genomics J1/2015 9 (c) Deoxyribonucleic Acids (DNA) (i) Structure  DNA molecule consists of 2 polynucleotide chains spiralled around an imaginary axis to form a double helix.  The 2 polynucleotide chains are antiparallel (run in opposite directions)  One strand runs in 5’ to 3’ direction.  The other strand runs in 3’ to 5’ direction.  DNA molecule has a uniform width of 2 nm.  The nitrogenous bases are stacked 0.34 nm apart and t