Chapter 3 The Origin of Molecules and the Nature of Life

1. Chapter 3The Origin of Moleculesand the Nature of Life Figure CO: Hot thermal spring

2. Overview of Molecular Evolution • Natural preconditions • Laboratory reproduction • Only on Earth? Elsewhere? • Specific locations? • RNA, DNA, proteins • “organic” molecules • Life = organisms?

3. Prerequisites for the Origin of Molecules • Our Sun and the Earth’s orbit (Goldilocks zone) • Sun provides steady radiant energy • Earth’s nearly circular orbit provides a relatively constant input of light energy (Goldilocks zones)

4. Figure 01: Various Molecules Observed in Molecular Clouds within Our Galaxy There is also much water, H2O, in the universe. Adapted from Buhl, D., Origins of Life 5 (1974): 29-40.

5. Prerequisites for the Origin of Molecules • Chemicals • Earth is chemically diverse, in part because it is part of young solar system • Carbon – an element well suited to be the structural basis of life • Water • Hydrogen and Oxygen • Universal solvent • Nitrogen, Sulfur, Phosphate, Iron, etc.

6. Elements Found on Earth • 92 occur naturally in nature • 24 occur naturally in the body • the most common: H, C, O, N vital elements for life

7. The Origin of Life • This is the cover of the first English edition (1938) of the pioneering work of the biochemist Aleksandr Ivanovich Oparin (1894-1981), published in Russian in 1924 (in English in 1936) • Oparin elaborated, within the framework of Darwinism, the first successful scientific approach to the problem of the origin of life, modernizing the old spontaneous generation controversy as a new hypothesis of Biogenesis (Abiogenesis)

8. Oparin’s The Origin of Life • Oparin’s book stands out as a milestone in science because no one had given serious thought to the problem of the origin of life after Louis Pasteur concluded in 1864 that life always came from pre-existing life • To account for life on the Earth, several leading scientists even proposed that the first forms of life were delivered to the Earth from elsewhere (panspermia), but Oparin’s basic premise was that living systems must have arisen from non-living chemicals on the early Earth

9. John Burdon Sanderson [J.B.S.] Haldane (1892-1964) • British contemporary of Oparin who independently proposed (1928) a similar hypothesis that conditions on the primitive Earth favored chemical reactions that synthesized organic compounds from inorganic precursors: biopoiesis • Haldane had also suggested that the earth's pre-biotic oceans – very different from their modern counterparts – would have formed a "hot dilute soup" in which organic compounds, the building blocks of life, could have formed – the “primordial organic soup” of early oceans, tidal pools or warm ponds

10. J.B.S. Haldane "Theories have four stages of acceptance. i) this is worthless nonsense; ii) this is an interesting, but perverse, point of view, iii) this is true, but quite unimportant; iv) I always said so.“ “J.B.S. Haldane was perhaps the most brilliant science populariser of his generation.” Arthur C. Clarke

11. Harold Urey & Stanley Miller In 1953, Harold C. Urey and his graduate student, Stanley L. Miller, at the University of Chicago conducted experiments that simulated hypothetical conditions present on the early Earth and test for the occurrence of chemical evolution

12. “Life” Sparked in Test Tubes: The Miller-Urey Experiments • Heated water, simulating vulcanism, produced water vapor circulating through the closed system of glass chambers • Miller and Urey placed gases into the upper chamber thought to be present in Earth’s early reducing atmosphere, and applied a repeating spark to simulate lightning

13. “Life” Sparked in Test Tubes: The Miller-Urey Experiments • Condensers cooled the gases and vapors, causing molecular reaction products to collect in the water • Samples were taken from this water over the next week and analyzed • Many simple and some surprisingly complex organic molecules were recovered

14. Miller-Urey Products • Among the organic molecules formed were amino acids, basic building blocks of protein • Subsequent follow-up trials, by many other biologists, using various combinations of “primitive atmospheres,” produced even more complex organic compounds • Sugars, lipids, and some of the building blocks for nucleic acids were also formed

15. Sidney Walter Fox (1912 - 1998) • In 1958 Fox and Kaoru Harada reported that heating dry amino acid mixtures to 180oC produced polymers resembling proteins • The dry heat actually melted the amino acids and baked out water molecules so that chemical bonds formed that linked the amino acids together into polymers they called thermal condensation products, or proteinoids 

16. Sidney Walter Fox (1912 - 1998) • In the 1960s, Fox and his collaborators found that under certain conditions proteinoids assembled into microscopic spherical balls, which they referred to as proteinoid microspheres • These were similar to the coacervate described by Oparin, and the fact that they were composed of amino acid polymers made them a more attractive model of a prebiotic protocell than the mixture of gelatin and gum arabic that Oparin had studied • Furthermore, dry heat seemed to be a very plausible energy source for driving condensation reactions

17. Chemical Development of Prebiotic Organic Compounds - How? coacervate droplets • Other simulation experiments can generate building blocks from the primordial soup • Miller and Urey formed amino acids • Gaseous H2, CH4 (methane), NH3(ammonia), H2O(steam) • Sparks (simulate atmospheric lightning) • Oparin and Fox formed protobionts, proteinoids, & microspheres (also called coacervate droplets) • These molecular collections mimic cell behavior, but are non-living

18. Replicating the Production of the First Molecules in the Laboratory • Miller-Urey type experiments continue to be carried out to this day, using a variety of ingredients and experimental conditions • Evolution of carbon-based molecules was not as unlikely an event as had previously been thought

19. Possible Sites for the Origin of the First Molecules on Earth • Hydrothermal vents • Thermophilic (heat-loving) organisms • Volcanoes • Sponge-like minerals (zeolites) that can retainand catalyze organic compounds • Clays • Layered clays served as polymerizing templates

20. Chemical Development of Prebiotic Organic Compounds -How? • Bada and Miller's “sub-ice organic gazpacho” theory (ice as a catalyst for abiosynthesis reactions) • Amino acids of extraterrestrial origin • Carbonaceous chondrite meteorites contain organic compounds, amino acids, fatty acids, etc. • Murchison Meteorite, Australia (L) and Allende Meteorite (~2 tons), Mexico (R)

21. What Came Next From thePrimordial Organic Soup? • Phospholipids (of an appropriate length) can spontaneously form lipid bilayers, a basic component of the cell membrane. • The polymerization of nucleotides into random autocatalytic RNA molecules might have resulted in self-replicating ribozymes (RNA world hypothesis). • Natural Selection pressures for catalytic efficiency and diversity result in ribozymes which catalyse peptidyl transfer (hence formation of small proteins), since oligopeptides complex with RNA to form better catalysts. Thus the first ribosome is born, and protein synthesis becomes more prevalent. • Proteins outcompete ribozymes in catalytic ability, and therefore become the dominant biopolymer. Nucleic acids are restricted to predominantly genomic use.

22. Increased Complexity of Organic Molecules - How? • Amino acids are monomers • Monomers must peptide bond to form proteins • This requires an input of energy and removal of water • How could this occur? • Evaporation? • Tidal pools? • Freezing? • Chemical dehydration? • Bonding to charged mineral surfaces? • Clays? Pyrites?

23. Biopoesis Again • Biologist John Desmond Bernal (1901-1971) coined the term Biopoesis for this process, and suggested that there were a number of clearly defined "stages" that could be recognized in explaining the origin of life in the 1960s. • Stage 1: The origin of biological monomers • Stage 2: The origin of biological polymers • Stage 3: The evolution from molecules to cell • Bernal suggested that evolution (natural selection) may have commenced early, some time between Stage 1 and 2.

24. Biopoesis in Three Stages

25. Biopoesis • Abiogenesis/Biopoesis remains an exciting area for current research

26. DNA, RNA and Proteins • Three fundamental classes of molecules are associated with modern life • Replication, transcription, translation Figure 03: DNA replicates and information is transferred from DNA to RNA to protein

27. Figure 02: Mutual Dependence of Information Carried by Nucleotide Sequences The mystery: which came first, DNA, RNA, or protein?

28. Which of These Molecules Evolved First: DNA, RNA or Protein? • DNA First? (“DNA World”) • Protein synthesis depends on the prior existence of RNA and DNA. • Proteins First? (“Protein World”) • Some amino acid polypeptides form without DNA. • RNA First? (“RNA World”) • RNA could catalyze chemical reactions and replicate

29. History of Chemistry forthe Origin of Life The RNA World refers to a hypothetical stage in the origin of life on Earth

30. It Was a Small RNA World After All • The phrase "The RNA World" was coined by Walter Gilbert in 1986 in a commentary on the then recent observations of the catalytic properties of various RNAs • However, the idea of independent RNA life is older and can be found in Carl Woese's book The Genetic Code (1967) • Five years earlier, the molecular biologist Alexander Rich, of the Massachusetts Institute of Technology, had posited much the same idea in an article

31. The RNA World • During the time of the RNA World, proteins were not yet engaged in biochemical reactions • RNA carried out both the information storage task of genetic information and the full range of catalytic roles necessary in a very primitive self-replicating system • Later RNA catalyzed the formation of DNA

32. Abiogenesis DNA RNA Other? RNA? Other?

33. Nucleic Acids DNA Replication RNAs Transcription Translation Were there other early lifeforms with other molecular mechanisms of inheritance beyond the “RNA world?” Who knows? Perhaps finding life elsewhere in the universe will demonstrate them? Quick Review

34. Nucleic Acids • DNA is the genetic material • made of 4 building blocks – nucleotides • adenine (A), guanine (G), cytosine (C), thymine (T) • A-T, C-G in the chain • double helix model • double stranded DNA • RNA carries hereditary information from nuclear DNA to the cytoplasm (inside cells) • uracil (U) replaces T • single stranded RNA Complimentary Base-Pairing

35. The Structure of the Genetic Material

36. DNA Forms a Template for Its Semiconservative Replication

37. DNA Replication • semi-conservative • helicase – unwinds DNA • DNA polymerases • one strand is the template • builds a complementary strand • bases pair with hydrogen bonds • A-T • C-G

38. DNA Replication Enzymes DNA Primase, DNA Replicase, DNA Polymerase III, DNA Polymerase I (DNA Polymerse II is a repair enzyme)

39. DNA Replication in a Bacterium • The circular bacterial DNA begins replication at a single site, the replication origin • Replication proceeds out in both directions, until copies of each strand of DNA are produced

40. Information Transfer—DNA to RNA to Protein • DNA triplets transcribed to produce complementary codon triplets in mRNA • Each mRNA codon triplet specifies a particular amino acid • Sequentially, codon by codon, the mRNA is a blueprint used in translation to produce a particular protein molecule

41. Three RNAs in Protein Synthesis • Different types of RNA play a different role in the synthesis of protein. • mRNA • rRNA • tRNA

42. Two StageProtein Synthesis • Transcription (in nucleus*) • DNA – gene blue print • triplet code - 3 bases/AA • template • exons - expressed • introns – excised • RNA – tools for protein synthesis • mRNA • tRNA • rRNA • Translation (in cytoplasm) • Ribosome • codons are read to build a primary protein structure * No nucleus in the prokaryotes

43. Transcription I

44. Transcription II Exons = coding sequences Introns = non-coding seqeunces

45. Translation Uses the Codon Dictionary The common code is possibly the strongest evidence of all for the common ancestry of all life on Earth

46. Translation at the Ribosome

47. In Organisms, Information Flows from DNA to RNA to Proteins The Central Dogma Of Molecular Biology The Genetic Code Is Universal and Redundant and Unambiguous

48. The Genetic Code • The code is universal because it specifies the same 20 amino acids in all organisms with only few exceptions • The code is redundant because there are multiple codons which code for the same AA • The code is unambiguous because any one codon codes for only one amino acid • The code is a triplet code because 3 bases represent a single AA in a codon

49. The Lac Operon The Lac Operon is a classic example of negative feedback gene regulation in prokaryotes

50. The Lac Operon • When lactose is absent then there is very little Lac enzyme production (the operator has LacI repressor bound to it) • When lactose is present but a preferred carbon source (like glucose) is also present then a small amount of enzyme is produced (LacI is not bound to the operator)