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Human genome sequence DNA = DEOXYRIBONUCLEIC ACID RNA = RIBONUCLEIC ACID Strong acid hydrolyses DNA & RNA into 3 components: • • • nitrogenous base (4 different ones) sugar phosphoric acid Mild acid hydrolyses DNA & RNA into 2 components: • • Nucleoside = base—sugar Nucleotide = base-sugar-phosphate DNA & RNA are polymers of nucleotides NUCLEOTIDE structure: nitrogenous bases 6 7 PURINE 5 1N N 8 2 N 3 amino NH2 4 N9 H N N ADENINE — A N N H O N HN GUANINE — G amino H2N keto (carbonyl) N N H NUCLEOTIDE structure 4 PYRIMIDINE 3N 5 2 6 N 1 CYTOSINE — C THYMINE — T NH 2 N amino O HN URACIL— U keto (carbonyl) CH3 O HN methyl O N H O N H keto (carbonyl) O N H First difference between DNA and RNA: DNA contains the bases A, G, C and T RNA contains the bases A, G, C and U NUCLEOTIDE structure 2. THE SUGARS — pentoses 5 HO CH2 D-ribose (RNA) O 1 4 H H 2 3 OH D-2-deoxyribose (DNA) OH 5 HO CH2 OH O OH 1 4 H H 2 3 OH OH H Second difference between DNA and RNA: DNA contains 2-deoxyribose RNA contains ribose NUCLEOTIDE structure 3. PHOSPHORIC ACID O O pH 7 HO P OH OH (H3PO4) Phosphoric acid O- P OH O- (HPO42-) Phosphate ion NUCLEOSIDE = base—sugar NH2 N N N N adenine DEOXYADENOSINE = adenine—deoxyribose HO CH2 O H H OH H OH deoxy ribose NUCLEOTIDE structure Base—sugar—phosphate NH2 N e.g. ADENOSINE N N O O- adenine 5' P HO OCH2 O O- Adenosine 5'-monophosphate (5'-AMP) N H H OH OH ribose NUCLEOSIDE numbering NH2 4 "Prime" mark: ' 5 N3 6 The 3' and 5' positions are very important for understanding DNA and RNA structure and function 2 N 1 5' HO CH2 O 1' 4' H H 3' 2' OH OH O Adenosine 5'-monophosphate (5'-AMP) NH2 Adenosine 5'-diphosphate (5'-ADP) N Adenosine 5'-triphosphate (5'-ATP) N N O - O P O- O O - OO P O- - OO N adenine 5' P HO OCH2 O OH H OH OH ribose How are mononucleotides linked together to form the polymers DNA and RNA? NH2 N 3',5'-phosphodiester bond O O N O 5' P HO OCH2 O- NH2 H O N H N 3' OH OH O O 5' P HO O CH2 O OH 3'OH H OH O POLARITY NH2 A N N N O O N C NH2 5' P HO O CH2 O N OH 3'OH H O N OH O O Single-stranded polynucleotides have one free 5' end and one free 3' end — they exhibit POLARITY C 5' P HO OCH2 O- NH2 H O N H N 3'OH OH O O 5' P HO OCH2 O OH 3'OH H OH O DNA is a double helix What information did Watson and Crick use in 1953 to arrive at their "double helix" structure for DNA? • Studies of DNA hydrolysis showed that the repeating unit was a NUCLEOTIDE • CHARGAFF's "rules" %A = %T %G = %C %A = %T %G = %C %G = %(C + 5-MeC) Plants have a particularly high content of 5-MeC Note that in addition to the bases A,G, C and T there are some minor bases found in DNA NH2 CH3 N O NHCH 3 N H 5-methylCYTOSINE prokaryotes and eukaryotes N N N N H 6-methylADENINE prokaryotes X-ray diffraction patterns obtained by Wilkins, Franklin & Gosling showed: helical structure with repeats at 0.34 and 3.4 nm 2 nm wide phosphates on outside of structure Density of chain suggests the helix contains 2 strands Conclusion: DNA MUST be double-stranded H H A N 3 H-bonds N N GC base pair H O N H3C N H H N H N G N O T AT base pair 2 H-bonds N O 1.08 nm H H N N N H H N N H H N C O H 1.08 nm Double helical DNA Minor groove Major groove 3.4 nm: One helical turn Base pairs "stacked" vertically in interior sugarphosphate backbone 0.34 nm 10 bp per turn 2 nm 2 nm Strands are Both strands coiled round a ANTIPARALLEL common axis One runs 5' to 3' 5' 3' 3' 5' Other runs 3' to 5' Watson & Crick solved the structure of DNA in 1953 "...A structure this pretty just had to exist." - James Watson in The Double Helix The implications of the ‘Double Helix’ Based on the fact that DNA is the genetic material: Stable Faithful replication and propagation of life – Two strands: one can form the template for DNA replication Faithful transmission of information to RNA – One strand acts as template RNA then transfers information to proteins http://science.nhmccd.edu/biol/bio1int.htm DNA replication Protein Structure Amino acid structure H H N H C R O C OH R is a chemical group that varies in different amino acids. C is central “chiral” carbon. Non-polar amino acids Polar amino acids Peptide bonds result from dehydration of A.A.s Primary structure is the sequence of A.A.s Sickle-cell anemia cause Secondary structure Tertiary structure Quaternary structure If all cells come from other cells where did the first ‘life’ come from? The Miller-Urey experiment Water is heated in a closed apparatus containing methane (CH4), ammonia (NH3) and hydrogen (H2) and an electric discharge is passed through the mixture. Many precursors can be produced in simple pre-biotic conditions • Some amino acids found (building blocks for proteins) • Some nucleic acids found e.g. adenine • Some sugars found including ribose