Toward a General Theory of Evolution

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

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

3. General Theory of Evolution Attempts to extend and reformulate Darwinian thinking in chemical terms to help bridge between biologicaland chemical worlds. • 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)

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

5. Replication Reaction is Autocatalytic Autocatalysis -can exhibit exponential growth • 79 replication cycles would convert a single molecule to a mole (279 ~ 6. 1023). • a further 83 cycles would generatea mass equal to that of the earth, 1027g! Replication is unsustainable 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) Replication is unsustainable, therefore for stability rate of replicator formation rate of decay ~ = dX/dt = kXM - gX X = replicator conc. M = monomer conc. k,g = rate constants. Lotka, 1910 dX/dt = 0 would define a steady state population If a replicating system is stable then its stability is of a dynamic kinetic kind

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 Replicator World: Dynamic kinetically Dynamic kinetically Less Stable More Stable A. Pross, J. Syst. Chem. 2011 A. Pross, Pure Appl. Chem. 2005

10. How Did Life Emerge? Chemical Phase Biological Phase Inanimate matter Simple Life Complex Life ? Darwinian theory One singlephysicochemical process initiated by simple replicating entity Process defined by drive toward greaterDKS A. Pross, J. Syst. Chem. 2011

11. Evidence for Single Process Both chemical and biological phases exhibit similar underlying patterns Replication Mutation Selection Evolution 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 (1) The essence of biology:

12. (2)Complexification 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. von Kiedrowski, Nature, 1994 self-replicating peptides M. R. Ghadiri et al., Nature, 1997 G. Ashkenasy et al., Chem. Eur. J, 2010

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

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

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

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

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

18. Evolutionary Sequence Traditional Darwinian sequence: Replication Mutation Selection Evolution New proposal: Replication Mutation Complexification SelectionEvolution 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 • For molecular replicators there is just one level of turnover • At cell level two levels of turnover Protein degradation and re-synthesis is a tightly regulated process. intracellular protein t1/2 =11 mins - 48 hrsHershko, Ciechanover & Rose (Nobel Prize, 2004) • 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. Q: How could the evolutionary process lead to the formation of thermodynamically unstable systems? A: In replicative world the stability that counts is dynamic kinetic stability (DKS). How can highstability of one kind lead to low stability of another kind?

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

25. Consequences of Metabolism • Metabolism (energy gathering) frees the replicator from thermodynamic constraints. • The result: Thermodynamically unstablebut dynamic kinetically stablereplicating entities • With thermodynamic constraints eliminated, primary directive for chemical change becomes kinetic rather than thermodynamic. • The moment lifebegan… • 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. Darwin’s Two Principles Principle of Natural Selection Principle of Divergence

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

29. Regular systems: History inaccessible Futurepredictable Implications of Different Topologies 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. • 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. Acknowledgements Prof. Emmanuel Tannenbaum – BGU Dr. Nathaniel Wagner – BGU Dr. NellaPross - BGU