2. The Origin of Life Collegium Budapest – Institute for Advanced Study A Centre for Excellence

3. But what is life? This may be a philosophical question This may be a philosophical question Better to ask what a living system is! Better to ask what a living system is! Autonomous life is always cellular Autonomous life is always cellular But there are several types of cell But there are several types of cell The main divide is between eukaryotes (cells with nuclei) and prokaryotes (bacteria) The main divide is between eukaryotes (cells with nuclei) and prokaryotes (bacteria)

4. The eukaryotic cell is very complex—too complex!

5. The simplest cells are bacterial THUS we want to explain the origin of some primitive bacterium-like cell Even present-day bacteria are far too complex The main problem is the genetic code

6. The major transitions (1995)

7. Origins of Life in Ravello (last year) Moderately peaceful coexistence of the churches Moderately peaceful coexistence of the churches The metabolists, the geneticists and the compartmentalists The metabolists, the geneticists and the compartmentalists Some synergistic complementation Some synergistic complementation Still not understood Still not understood

8. Units of evolution (JMS) hereditary traits affecting survival and/or reproduction 1.multiplication 2.heredity 3.variation

9. A crude picture (Deamer)

10. The prebiotic soup (Oparin— Haldane, Miller) Electric discharge and heating Electric discharge and heating Strongly reducing atmosphere (water, methane, ammonia, etc.) Strongly reducing atmosphere (water, methane, ammonia, etc.) No evidence for strong reduction No evidence for strong reduction Decreased reducing power decreases yield Decreased reducing power decreases yield Chemical incompatibility Chemical incompatibility

11. Chemical incompatibility condition a  substance A condition a  substance A condition b  substance B condition b  substance B does NOT imply that does NOT imply that Condition (a+b) is feasible, OR that Condition (a+b) is feasible, OR that Condition (a+b)  substances (A+B) Condition (a+b)  substances (A+B) Most formidable example: tar formation Most formidable example: tar formation

12. We need the (mineral) surface! Bernal, Wächtershäuser Bernal, Wächtershäuser Thermodynamic effect: A(bound) + B(bound)  C(bound) + D(leaving) Thermodynamic effect: A(bound) + B(bound)  C(bound) + D(leaving) Entropy is on your side Entropy is on your side Kinetic effect: surface catalysis Kinetic effect: surface catalysis Population structure  modifies the outcome of natural selection Population structure  modifies the outcome of natural selection

13. Prebiotic pizza (Wächtershäuser)

14. The formose ‘reaction’ formaldehyd e glycolaldehyde autocatalysi s Butlerow, 1861

15. Replication in the formose reaction Replication is non-informational Replication is non-informational Autocatalysis – YES Autocatalysis – YES Heredity – NO Heredity – NO Good for metabolism Good for metabolism Not good for genetics Not good for genetics

16. The iron-sulphur world High pressure/high temperature High pressure/high temperature Pyrite surface Pyrite surface Underwater hydrothermal vents Underwater hydrothermal vents Reducing power (H 2 S) Reducing power (H 2 S) Pyruvic acid (CH 3 -CO-COOH) decomposes at 165 C normally, but forms at 250 C under high pressure! Pyruvic acid (CH 3 -CO-COOH) decomposes at 165 C normally, but forms at 250 C under high pressure! Largely unknown chemistry (astrobiology) Largely unknown chemistry (astrobiology) An ancient reductive citric acid cycle? An ancient reductive citric acid cycle?

17. Von Kiedrowski’s replicator

18. SPREAD for replication (von Kiedrowski)

19. Classification of replicators Limited heredity Unlimited heredity Holisticformose Modular Von Kiedrowski genes Limited(# of individuals)  (# of types) Umlimited(# of individuals) << (# of types)

20. Interlude: the RNA world This idea goes back to Woese, Crick and Orgel This idea goes back to Woese, Crick and Orgel If ribonucleic acid (RNA) is able to catalyse reactions then we do not need a genetic code If ribonucleic acid (RNA) is able to catalyse reactions then we do not need a genetic code Credibility of this idea has been increasing in the past decade Credibility of this idea has been increasing in the past decade

21. RNA structures in 3 dimensions

22. Early replication is still a problem (the ‘Holy Grail’) Small replicators spontaneously undergo template replication Small replicators spontaneously undergo template replication Template and copy spontaneously dissociate Template and copy spontaneously dissociate Longer replicators stick together: not recursive Longer replicators stick together: not recursive Nonenzymatic replication is extremely limited Nonenzymatic replication is extremely limited A selected ribozyme can copy up to 14 nucleotides A selected ribozyme can copy up to 14 nucleotides That ribozyme is longer than 100 nt! That ribozyme is longer than 100 nt!

23. Eigen’s paradox (1971) Early replication must have been error- prone Early replication must have been error- prone Error threshold sets the limit of maximal genome size to <100 nucleotides Error threshold sets the limit of maximal genome size to <100 nucleotides Not enough for several genes Not enough for several genes Unlinked genes will compete Unlinked genes will compete Genome collapses Genome collapses Resolution??? Resolution???

24. Molecular hypercycle (Eigen, 1971) autocatalysis heterocatalytic aid

25. Parasites in the hypercycle parasite short circuit

26. Population structure is necessary! Good-bye to the well-stirred flow reactor Good-bye to the well-stirred flow reactor Adhesion to surface or compartmentation Adhesion to surface or compartmentation Hypercycles (with more than 4 members) spiral on the surface and resist parasites, BUT Hypercycles (with more than 4 members) spiral on the surface and resist parasites, BUT Are not resistant to short-circuits Are not resistant to short-circuits Collapse if the adhesive surface is patchy Collapse if the adhesive surface is patchy Only compartmentation saves them Only compartmentation saves them

27. A ‘metabolic’ system on the surface (2000)

28. A cellular automaton simulation Reaction: template replication Diffusion (Toffoli- Margolus algorithm) Metabolic neighbourhood respected Metabolic Replication Grey sites: neighbourhood Black: empty site X: potential mothers

29. Parasite on metabolism Parasites do not kill the system Can be selected for to perform useful function

30. Nature 420, 360-363 (2002).

31. Increase in efficiency Target and replicase efficiency Copying fidelity Trade-off among all three traits: worst case

32. Evolution of replicases on the rocks All functions coevolve and improve despite the tradeoffs Increased diffusion destroys the system

33. ‘Stationary’ population parasites efficient replicases

34. Evolving population Error rate Replicase activity

35. Compartmentation: a combined model membrane replicas e metabolic gene

36. Bubbles and permeability We do not know where lipids able to form membranes had come from!!!

37. The stochastic corrector model for compartmentation Szathmáry, E. & Demeter L. (1987) Group selection of early replicators and the origin of life. J. theor Biol. 128, 463-486. Grey, D., Hutson, V. & Szathmáry, E. (1995) A re-examination of the stochastic corrector model. Proc. R. Soc. Lond. B 262, 29-35.

38. Dynamics of the SC model Independently reassorting genes Independently reassorting genes Selection for optimal gene composition between compartments Selection for optimal gene composition between compartments Competition among genes within the same compartment Competition among genes within the same compartment Stochasticity in replication and fission generates variation on which natural selection acts Stochasticity in replication and fission generates variation on which natural selection acts A stationary compartment population emerges A stationary compartment population emerges

39. Group selection of early replicators Many more compartments than templates within any compartment Many more compartments than templates within any compartment No migration (fusion) between compartments No migration (fusion) between compartments Each compartment has only one parent Each compartment has only one parent Group selection is very efficient Group selection is very efficient Selection for replication synchrony Selection for replication synchrony

40. Principles of the Living State by Tibor Gánti First Hungarian edition 1971 First Hungarian edition 1971 Papers in BioSystems and JTB Papers in BioSystems and JTB Referenced by others Referenced by others Oxford University Press edition 2003 Oxford University Press edition 2003 Annotated by James Griesemer & E. S. Annotated by James Griesemer & E. S.

41. Gánti’s chemoton model metabolism template copying membrane growth Something like this we want to synthesize some day

42. Egalitarian and fraternal transitions (Queller, 1997)

43. Increase in complexity

44. “I have been always confused about this but now I’m confused on a higher plain” (Hamilton)