Nucleic Acids & The RNA World

1. Nucleic Acids & The RNA World Chapter 4 Biology 11

3. DNA vs. RNA Structure • DNA contains a deoxyribose at the 2’ carbon • RNA contains a ribose at the 2’ carbon • DNA bases • A, T, G, & C • RNA bases • A, U, G, & C

4. Nucleotide Structure • This is a monomer unit • Putting thousands, millions, or trillions of these together makes up the polymers of DNA or RNA

5. Chemical Evolution of the Nucleotide • Miller like lab simulations show that nitrogenous bases and many sugars can be synthesized under conditions that mimic the prebiotic soup • However, how did ribose become the dominant sugar • Ribose molecules may have been selectively enriched from the mix of sugars in early deep-sea vents

6. Chemical Evolution of the Nucleotide • Researchers simulated the conditions that exist in those vents • Minerals such as phosphate are able to bind sugars • Found that the minerals preferentially bound to ribose over other pentoses and hexoses • Ribose enrichment • However, a problem still remains with the synthesis of all the nucleotides

7. Nucleotide Polymerization • All polymerizations occurs in the 5’ to 3’ directions • Formed by phosphodiester linkage • Do not confusion the direction of chain elongation (5’ to 3”) with the actual biochemistry of the reaction which has the 3’ hydroxyl attack the 5’ phosphate of the new nucleotide

8. Nucleotide Polymerization

9. Is a polypeptide chain directional? Explain how In DNA or RNA one end has an unlinked 5’ phosphate while the other has an unlinked 3’OH The order of nitrogen bases forms the primary structure of the molecule and is different for every species DNA and RNA are Directional

10. Polymerization Energetics • Endergonic Process • In cells the free energy of the nucleotide monomers is raised by an additional two phosphate groups • Nucleotide triphosphates • Polymerization results in the release of pyrophosphate PPi

11. Polymerization Reaction Hydrolyzed by inorganic pyrophosphatase Releases 19 kJ/mol Releases 46kJ/mol

12. Could Polymerization have formed in the Absence of Cellular Enzymes • Researchers have produced RNA molecules by incubating nucleotides with mineral particles • Up to 50 nt long • In another experiment RNA molecules reached up to 100 nt in length • However, in this experiment lipids were added to help the molecules interact

13. DNA Polymerase

14. DNA Structure • 1953 James Watson and Francis Crick presented the model for DNA secondary structure • What they knew • Chemist had worked out the structure of nucleotides and knew about phosphodiester linkage & the sugar phosphate backbone • Knew of Chargaff rule • A=T, G=C & Ratio of purines and pyrimidines is the same • Knew of Rosalind Franklind X – Ray scatter pattern • Three repeated numbers • .34nm, 2.0nm, & 3.4nm • Surmised that DNA must have a repeating structure

15. DNA Structure • Bond angles & measurements suggested the 2.0nm was the width of the helix • 0.34 was the distance between single stacked bases • 3.4nm is 10X the distance between single pair of bases • Repeating spiral

16. DNA Structure • Watson and Crick made many models which did not accurately reflect the data • Finally they hit a model which seemed promising • Antiparallel backbone • Purine must pair with pyrimidine • Bases lined up in such a way that hydrogen bonding could only occur between certain purines with certain pyrimidines • Twisting necessary for hydrogen bonding • Twisting gave rise to major groves and minor groves • Minimizes contact between the bases and water • Bases stack on top of one another to make a hydrophobic interior difficult to break apart • Molecule as a whole is water soluble because of the backbone

17. DNA Structure

18. DNA Structure

19. Does DNA structure Correlate with it’s Function • “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism • But DNA can not copy itself • Not a catalytic molecule

20. Stability of DNA • The double helix is highly structured • Few functional groups are exposed to the outside • Lacks a 2’ hydroxyl group that RNA has making it much more stable • Good repository to store genetic information • Inept at catalysis • Regular and symmetric

21. DNA Function • DNA contains information required for an organism to grow and reproduce • The structure of DNA allow the molecule to copy itself • Hydrogen bonds separated • Two template strands

22. Two Key Differences No Thymine Uses a ribose with a 2’OH Therefore, when RNA folds in certain ways the hydroxyl group can attack the phosphate linkage breaking the backbone Less stable but can act as a catalytic molecule RNA

23. RNA Molecules & Tertiary Structure • When secondary structurefold into more complex shapes • Structurally and chemically RNA is intermediate between the complexity of proteins and the simplicity of DNA

24. RNA & Catalysis • Ribozymes • RNA can catalyze a limited number of chemical reactions • An RNA molecule from a single celled organism was isolated (Tetrahymena) • It can catalyze both the hydrolysis and the condensations of the phosphodiester linkages of RNA • Other reactions • Amino acid peptide bond formation • Intron splicing

25. Implications • The RNA world may be the key to the beginning of life and natural selection • Information • Replication • Evolve – random changes to base sequences