1. Toward a General Theory of Evolution Addy Pross Department of Chemistry, Ben Gurion University Be’er Sheva, Israel ILASOL - Dcember 25, 2011

2. How did life emerge? How to make life ? What is life? Chemistry-Biology Interface Problematic Still struggling to answer central life questions

3. General Theory of Evolution  Based on the unique kinetic character of the replication reaction  Identifies a stability kind associated solely with replicating entities - dynamic kinetic stability A. Pross (2003-11) Attempts to extend and reformulate Darwinian thinking in chemical terms to help bridge between biological and chemical worlds.

4. Molecular Replication A + B + C + ….. T T Molecular Replication Template mechanism S. Spiegelman, 1967 G. von Kiedrowski, 1986 L. Orgel, 1987 J. Rebek, 1994 M.R. Ghadiri, 1996 G. F. Joyce, 1997 e.g., nucleic acids, peptides, synthetic molecules

5. Replication Reaction is Autocatalytic  79 replication cycles would convert a single molecule to a mole (2 79 ~ 6. 10 23 ).  a further 83 cycles would generate a mass equal to that of the earth, 10 27 g! Replication is unsustainable Autocatalysis - can exhibit exponential growth T. Malthus, An Essay on the Principle of Population, 1798

6. Nature of Stability A system is stable if it is persistent, unchanging over time. Thermodynamic Stability – an inherent property of a chemical system Kinetic Stability – depends on reaction rates and barrier heights Dynamic Kinetic Stability - A stability kind associated solely with replicating entities. A. Pross, J. Syst. Chem. 2011 A. Pross, Chem. Eur. J. 2009

7. Dynamic Kinetic Stability (DKS) dX/dt = kXM - gX dX/dt = kXM - gX X = replicator conc. M = monomer conc. k,g = rate constants. Lotka, 1910 steady state population dX /dt = 0 would define a steady state population If a replicating system is stable then its stability is of a dynamic kinetic kind Replication is unsustainable, therefore for stability rate of replicator formation rate of decay ~ =

8. Stability in ‘Regular’ and Replicative Worlds  ‘Regular’ chemical systems are stable because they DO NOT react.  Replicating chemical systems are stable (persistent) because they DO react – to make more of themselves! DKS would apply to all stable replicating systems, biological and chemical. A.Pross, Pure Appl. Chem. 2005

9. Selection Rules in ‘Regular’ Chemical and Replicator Worlds ‘Regular’ Chemical World: Thermodynamically Thermodynamically Less Stable More Stable Less Stable More Stable Replicator World : Dynamic kinetically Dynamic kinetically Dynamic kinetically Dynamic kinetically Less Stable More Stable Less Stable More Stable A. Pross, J. Syst. Chem. 2011 A. Pross, Pure Appl. Chem. 2005

10. How Did Life Emerge? Simple Life LifeComplex BiologicalPhase ChemicalPhase Darwinian theory theory ? One single physicochemical process initiated by simple replicating entity Process defined by drive toward greater DKS Inanimate matter A. Pross, J. Syst. Chem. 2011

11. Evidence for Single Process Replication Mutation Selection Evolution Same pattern observed at chemical (molecular) level Same pattern observed at chemical (molecular) level e.g., RNA oligomers in a test-tube S. Spiegelman et al., PNAS, 1967 D.P. Bartel, J.W. Szostak, Science, 1993 M.C. Wright, G.F. Joyce, Science, 1997 Both chemical and biological phases exhibit similar underlying patterns (1) The essence of biology:

12. Biological level: Biological level: prokaryotes evolved into eukaryotes single cells evolved into multi-cell organisms emergence of ecological networks Chemical (molecular) level: emergence of cross-catalytic networks e.g., self-replicating DNA oligomers D. Sievers, G. D. Sievers, G. von Kiedrowski, Nature, 1994 (2) Complexification self-replicating peptides M. R. Ghadiri et al., Nature, 1997 G. Ashkenasy et al., Chem. Eur. J, 2010

13. G.F. Joyce, T.A. Lincoln, Science, 2009 Complexification Enhances RNA Replication Fast replication, self-sustained exponential growth Slow replication, limited exponential growth Complexification enhances replicating ability at the molecular level! A’ + B’ A + B Autocatalysis Cross-catalysis A + B T T E E’ E

14. Complexification Principle I’ll scratch your back if you’ll scratch mine…. Complexification enhances replicating ability at both chemical and biological levels - network formation. Cooperation = Complexification

15. Unification of Chemical and Biological Phases Simple Life Complex Life Chemical phase Simple Replicating System One continuous process Biological phase Low complexityHigh complexity One process – one set of principles Greater complexity is induced by the drive toward greater DKS A. Pross, J. Syst. Chem. 2011

16. Darwinian ConceptsChemical Concepts natural selection natural selection adaptation adaptation dynamic kinetic stability (DKS) dynamic kinetic stability (DKS) survival of the fittest drive toward greater DKS survival of the fittest drive toward greater DKS Darwinian concepts firmly rooted in chemistry A.Pross, J. Syst. Chem. 2011 A.Pross, Chem. Eur. J. 2009 Darwinian concepts - Particular applications of broader chemical concepts kinetic selection kinetic selection fitness

17. General Theory of Evolution  Driving force - toward greater DKS  Mechanisms - complexification (primary) - selection (secondary) - selection (secondary) A. Pross, J. Syst. Chem. 2011 Extended theory embraces both biological and chemical systems

18. Evolutionary Sequence Replication Mutation Selection Evolution Replication Mutation Selection Evolution Traditional Darwinian sequence: Traditional Darwinian sequence: Replication Mutation Complexification New proposal: SelectionEvolution Selection Evolution Martin Nowak (2011): Cooperation – the third evolutionary principle in addition to mutation and selection “Supercooperators”, 2011

19. Global Characteristics of Living Systems  Extraordinary complexity  Dynamic character  Far-from-equilibrium state  Teleonomy (purposeful nature)  Homochiral character  Diversity Can be understood through the DKS concept A. Pross, J. Sys. Chem. 2011

20. Dynamic Kinetic Stability (DKS)

21. Dynamic Steady States Exist at Various Levels of Complexity  At cell level two levels of turnover Protein degradation and re-synthesis is a tightly regulated process. intracellular protein t 1/2 = 11 mins - 48 hrs Hershko, Ciechanover & Rose (Nobel Prize, 2004)  For molecular replicators there is just one level of turnover  At the organismic level three levels of turnover

22. Global Characteristics of Living Systems  Extraordinary complexity  Dynamic character  Far-from-equilibrium state  Teleonomy (purposeful nature)  Homochiral character  Diversity Can be understood through the DKS concept A. Pross, J. Sys. Chem. 2011

23. A: In replicative world the stability that counts is dynamic kinetic stability (DKS). How can high stability of one kind lead to low stability of another kind? Q: How could the evolutionary process lead to the formation of thermodynamically unstable systems?

24. A Key Step on Road to Complexity - Incorporating a Metabolic Capability Metabolism = energy gathering capability Non-Metabolic Metabolic Replicator Replicator Dynamic Kinetically Dynamic Kinetically less stable more stable N. Wagner, A.Pross, E.Tannenbaum, Biosystems, 2010 Metabolism is kinetically selected for

25. Consequences of Metabolism  Metabolism (energy gathering) frees the replicator from thermodynamic constraints.  The result: Thermodynamically unstable but dynamic kinetically stable replicating entities  With thermodynamic constraints eliminated, primary directive for chemical change becomes kinetic rather than thermodynamic. The moment life began…  Death – reversion to the thermodynamic world

26. Global Characteristics of Living Systems  Extraordinary complexity  Dynamic character  Far-from-equilibrium state  Teleonomy (purposeful nature)  Homochiral character  Diversity Can be understood through the DKS concept A. Pross, J. Sys. Chem. 2011

27. Principle of Natural Selection Principle of Divergence Darwin’s Two Principles

28. ‘Regular’ (thermodynamic) Space Topology of ‘Regular’ Chemical and Replicator Spaces Thermodynamic sink Replicator (kinetic) Space ConvergentDivergent Topology of replicator space explains diversity A. Pross, J. Syst. Chem. 2011 DKS clarifies Darwin’s Principle of Divergence

29. Implications of Different Topologies Regular systems: History inaccessible Futurepredictable Future predictable Replicators: History accessible Future unpredictable N. Wagner, A. Pross, Entropy 2011 A. Pross, Pure Appl. Chem. 2005

30. Key Conclusions DKS - the conceptual bridge between Chemistry and Biology. 30 Unifies abiogenesis and biological evolution Integrates Darwinian theory into general chemical theory DKS – the driving force for evolution Explains life’s unusual characteristics Life - an ever expanding dynamic network of chemical reactions derived from the replication reaction.

31. Prof. Emmanuel Tannenbaum – BGU Dr. Nathaniel Wagner – BGU Dr. Nathaniel Wagner – BGU Dr. Nella Pross - BGU Dr. Nella Pross - BGU Acknowledgements