Nucleic Acids and the RNA World

1. Nucleic Acids and the RNA World Pages 74-89 Chapter 4

2. RNA vs. Protein • Chemical Evolution stated that life evolved from a polymer called a protein. • HOWEVER, now many scientists question this. • There is currently a large scientific motion towards a polymer called a Nucleic Acid. • Specifically, a RiboNucleic Acid • RNA

3. RNA World Hypothesis • This proposal is called the RNA World Hypothesis • Again, this is still very HYPOTHetical • THIS IS THE DELEMA OF LIFE

4. What is Life????? • This is an age old question that scientists still debate! • We don’t have a simple explanation, and therefore discussing the origin of life is nearly impossible • There are 2 versions of the story… • We will need to use the 2nd version

5. Version 1 (The easy version) • 1. All life is made of cells • 2. Life reacts to its environment • 3. Life reproduces • 4. Life uses energy • 5. Life grows at some point • Sadly…..it isn’t so cut and dry!

6. Version 2 (Our version) • Because scientists constantly debate this issue, we only use two of these rules to discuss LIFE in high end Biology • 1. The ability to reproduce! • 2. The ability to acquire particular molecules and use them in CONTROLLED CHEMICAL REACTIONS that maintain conditions suitable for life & contribute to growth!

7. What About the Other 3 Requirements • They are there…. They are just used as subcategories at this level of Biology. • IE: Chemical reactions (Rule 2) are precisely controlled because chemicals and reactants are bound by a Plasma Membrane. • Therefore, it is required for life… it is just no longer the rule! • The problem is that if it is debated, it becomes an uncertain theory • Remember, even the “rules” are JUST theories

8. All Polymers are Proteins? • Thus far, every polymer we have learned about IS a protein. • HOWEVER, we now are learning of a new polymer. • Proteins are the result of polymerization of monomers called Amino Acids • Nucleic Acids are the result of polymerization of monomers called Nucleotides

9. Nucleotide

10. Components of a Nucleotide • 3 components • Phosphate group • Sugar • Nitrogenous (Contains a nitrogen) Base • PAGE 75 Nitrogenous Base Phosphate Sugar

11. Sugar • Your sugar is an organic compound with a carbonyl group • C=O

12. How do Nucleotides Polymerize • Figure 4.2 on page 76 • It starts with a phosphodiester linkage • This condensation reaction is the formation of the bond between the phosphate group of one nucleotide and the hydroxyl group of the sugar component. • If the nucleotides involved contain the sugar RIBOSE, the polymer is called RNA • If the nucleotides involved contain the sugar DEOXYRIBOSE, the polymer is called DNA

13. DNA’s Sugar-Phosphate Backbone

14. RNA’s Sugar Phosphate Backbone

15. Count Your Primes

16. Base Pairs

17. Base Pairs

18. Base Pairs Adenine

19. Base Pairs Guanine

20. Base Pairs Thymine

21. Base Pairs Cytosine

22. Chargaff’s Theory • Found that the #of bases (Purines & Pyrimidines) are the same • The # of A’s = # of T’s • The # of C’s = # of G’s • Found that these bases must be relavent to its matching pair

23. WATSON and CRICK • Announced in 1953 • Used the results of other scientists to figure out the structure of DNA

24. Watson & Crick Model • Chemists found that DNA polymerized through the formation of phosphodiester linkages • This concluded a sugar-phosphate backbone • By analyzing the total number of purines and pyrimidines it was found that the number of A’s and T’s were equal to the number of C’s and G’s • This was called Chargaff’s rule after Erwin Chargaff • X-ray diffraction showed a repeating scatter pattern (.34 nm, 2.0nm, 3.4nm) • This repeating pattern only makes sense if the molecule is shaped as a double helix • Pages 79-82

25. Scatter Pattern X-ray Diffraction

26. Wilkins & Franklin • These measurements were from brilliant work done by Rosalind Franklin from King’s College • Franklin, who was a leader in the field of X-ray crystallography, worked in Maurice Wilkins Lab • Maurice Wilkins was the man charged with finding the structure of DNA in England • Wilkins and Franklin were not friends… But Wilkins, Watson, and Crick were friends… • Let the soap opera of science begin… … …

28. Scatter Pattern X-ray Diffraction • Watson & Crick began to analyze the size and geometry of deoxyribose, phosphate groups, and nitrogenous bases. • Using things like bond angles, and measurements, they were able to devise 2.0nm probably represented the width of the helix, and .34 was likely the distance between bases stacked in the spiral • They arranged two strands of DNA running in opposite directions (5`-3` and 3`-5`)

29. Base Pairing • Using the x-ray diffraction patterns and measurements, it was found only to work if: • Adenine always bonded with Thymine • Guanine always bonded with Cytosine • This phenomena is called Complimentary Base Pairing

31. Polarity of DNA • DNA is put together like a ladder with the sugar-phosphate bonds form the supports and the base pais form the rungs of the ladder • The tight packing of the nitrogenous bases are the hydrophobic interior that is hard to break apart • The exterior, sugar-phosphate backbone IS, however, hydrophilic, causing the molecule to be water soluble

32. Major vs. Minor Grooves Minor Groove Major Groove

33. Letters of a Book • Watson & Cricks Model of DNA was revolutionary because it explained how DNA worked • In the structure of DNA alone we can see how the different sequences of bases in DNA act like the letters in a book A-T = C-G

34. DNA Size • Width of the helix = 2.0nm • Length of one full complete turn of helix = 3.4nm • Distance between bases = .34nm

35. DNA Size

36. PROBLEM with DNA • As we have mentioned, DNA seems like a great suspect for the first polymer to reproduce itself • ONE PROBLEM • DNA is WAYYYYYyyyyy to simple and stable of a template act as a catalyst and fuel self replication • In fact, never has it been observed to act as a catalyst in the laboratory… • Which means, without an external energy source, DNA is very unlikely to be able to sustainably self replicate • And with the problem that “DNA doesn’t just replicate” what could it be???

37. RNA as a suspect for life • ….as a possible suspect for life’s “roots” • … … Or maybe first we should ask… What about RNA??? What is RNA?

38. DNA vs. RNA • Both have a sugar phosphate backbone formed by phosphodiester linkages • However there are 2 main differences: • The pyrimidine base THYMINE does not exist in RNA. Instead, RNA contains the the closely related pyrimidine base URACIL • The sugar in the sugar-phosphate backbone of RNA is RIBOSE, not deoxyribose as in DNA

39. RNA • The second point is CRITICAL when comparing the two (and understanding RNA) • The hydroxyl group on the 2`-carbon of RIBOSE is MUCH more reactive • This is the main difference that makes DNA stable and RNA reactive • The absence of Thymine and presence of Uracil makes them easy to distinguish

40. RNA Hairpin • Another difference between RNA and DNA is in their secondary structures • Very often, RNA is denoted as a single strand (where DNA is a double strand) • However, RNA can appear to be a double stranded helix during what is called a Hairpin • This is when the secondary structure of RNA loops and forms a double stranded “stem”

41. RNA Hairpin

42. Hairpins • These form WITHOUT energy input because they exergonic • Hydrogen bond formation is exothermic and exergonic • Though they do release the entropy of the strand, this is a “flag” for being the first reproducing molecule because it can release bond energy required for replication

43. RNA Contains Information • RNA contains a sequence of bases that is analogous to the letters in a word • This allows it to carry information • Because hydrogen bonding occurs specifically between A-U and G-C in RNA, it is THEORETICALLY possible that it can make a copy of itself • Figure 4.14

44. Template & Complimentary • When considering the replication process, it is important to know the terminology for each strand • Template Strand: Original strand • Complimentary Strand: New strand being created • It is called this because it needs to match the template as a perfect compliment

46. DNA Replication • DNA is not only an exceptional information carrying molecule; it is also structurally made to replicate itself • Through simple base pairing, DNA basically has two copies at all time • All DNA polymerase (the protein that helps form the new DNA strand) has to do is unzip the molecule • Once the molecule is unzipped, deoxyribose nucleotides will naturally make new base pairs

47. DNA polymerase works in a 5’-3’ direction 3’ 5’ Lagging Strand Leading strand 3’ 5’

48. Leading & Lagging • Where the DNA strand is unzipped is known as the replication fork • From this fork, each of the original strands acts as a template for replication • The leading strand allows the new strand synthesized complementary to it, to be synthesized 5' to 3' in the same direction as the movement of the replication fork. • The lagging strand starts away from the replication fork (moving towards it) and adds small fragments to template strand called Okazaki fragments • DNA polymerase works in a 5’-3’ direction