Toward a General Theory of Evolution

Toward a General Theory of EvolutionToward a General Theory of Evolution

Addy ProssDepartment of Chemistry, Ben Gurion University

Be’er Sheva, Israel

ILASOL - Dcember 25, 2011

How did life

emerge?

How to make

life?

What is life?

Chemistry-Biology Interface Chemistry-Biology Interface ProblematicProblematic

Still struggling to answer central life questions

General Theory of EvolutionGeneral 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.

Molecular ReplicationMolecular Replication

A + B + C + …..A + B + C + ….. T T Molecular Molecular

ReplicationReplication

Template mechanism

S. Spiegelman, 1967G. von Kiedrowski, 1986

L. Orgel, 1987 J. Rebek, 1994

M.R. Ghadiri, 1996G. F. Joyce, 1997

e.g., nucleic acids, peptides, synthetic molecules

Replication Reaction is Replication Reaction is AutocatalyticAutocatalytic

79 replication cycles would convert a single 79 replication cycles would convert a single molecule to a mole (molecule to a mole (227979 ~ 6. 10 ~ 6. 102323).).

a further 83 cycles would generate a mass a further 83 cycles would generate a mass equal to that of the earth, equal to that of the earth, 10102727gg!!

Replication is unsustainable

Autocatalysis - can exhibit exponential growth

T. Malthus, An Essay on the Principle of Population, 1798

Nature of StabilityNature of StabilityA system is stable if it is persistent ,

unchanging over time.

Thermodynamic Stability – an inherent property of a chemical systemKinetic Stability – depends on reaction rates and barrier heights

Dynamic Kinetic Stability - A stability kind associated solely with replicating entities.

A. Pross, J. Syst. Chem. 2011A. Pross, Chem. Eur. J. 2009

Dynamic Kinetic Stability (DKS)Dynamic Kinetic Stability (DKS)

dX/dt = kXM - gXdX/dt = kXM - gXX = replicator conc.X = replicator conc.M = monomer conc.M = monomer conc.k,g = rate constants.k,g = rate constants.

Lotka, 1910Lotka, 1910

dX/dt = 0 would define a steady state steady state populationpopulation

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 ~=

Stability in ‘Regular’ and Stability in ‘Regular’ and Replicative WorldsReplicative Worlds

‘‘Regular’ chemical systems are stable Regular’ chemical systems are stable because they because they DO NOTDO NOT react. react.

Replicating chemical systems are stable Replicating chemical systems are stable (persistent) because they (persistent) because they DODO react – to make react – to make more of themselves!more of themselves!

DKS would apply to all stable replicating systems, biological and chemical.

A.Pross, Pure Appl. Chem. 2005

Selection Rules in ‘Regular’ Selection Rules in ‘Regular’ Chemical and Replicator WorldsChemical and Replicator Worlds

‘‘Regular’ Chemical WorldRegular’ Chemical World::Thermodynamically Thermodynamically Thermodynamically Thermodynamically

Less Stable Less Stable More Stable More Stable

Replicator WorldReplicator World::

Dynamic kineticallyDynamic kinetically Dynamic kinetically Dynamic kinetically Less Stable Less Stable More StableMore Stable

A. Pross, J. Syst. Chem. 2011A. Pross, Pure Appl. Chem. 2005

How Did Life EmergeHow Did Life Emerge??

Simple Simple LifeLife

ComplexComplex LifeLife

Biological Biological PhasePhase

ChemicalChemicalPhasePhase

DarwinianDarwinian theorytheory??

One single physicochemical process initiated by simple replicating entity

Process defined by drive toward greater DKS

Inanimate Inanimate matter matter

A. Pross, J. Syst. Chem. 2011

Evidence for Single ProcessEvidence for Single Process

Replication Mutation Selection EvolutionReplication Mutation Selection Evolution

Same pattern observed at chemical (molecular) levelSame pattern observed at chemical (molecular) levele.g., RNA oligomers in a test-tubee.g., RNA oligomers in a test-tube

S. Spiegelman et al., S. Spiegelman et al., PNASPNAS, 1967, 1967D.P. Bartel, J.W. Szostak, D.P. Bartel, J.W. Szostak, ScienceScience, 1993, 1993M.C. Wright, G.F. Joyce, M.C. Wright, G.F. Joyce, ScienceScience, 1997, 1997

Both Both chemical chemical and and biologicalbiological phases phases exhibit similar underlying patternsexhibit similar underlying patterns

(1)(1) The essence of biology: The essence of biology:

Biological level:Biological level: prokaryotes evolved into eukaryotes prokaryotes evolved into eukaryotes single cells evolved into multi-cell organismssingle cells evolved into multi-cell organismsemergence of ecological networks emergence of ecological networks

ChemicalChemical (molecular) level:(molecular) level:emergence of cross-catalytic networksemergence of cross-catalytic networkse.g., e.g., self-replicating DNA oligomersself-replicating DNA oligomers

D. Sievers, G. D. Sievers, G. von Kiedrowski, Nature, 1994

(2)(2) ComplexificationComplexification

self-replicating peptides

M. R. Ghadiri et al., Nature, 1997 G. Ashkenasy et al., Chem. Eur. J, 2010

G.F. Joyce, T.A. Lincoln, Science, 2009

Complexification Enhances Complexification Enhances RNA ReplicationRNA 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 TT

E

E’E

E’

Complexification PrincipleI’ll scratch your back if you’ll scratch mine….

Complexification enhances replicating ability at both chemical and biological levels - network formation.

Cooperation = Complexification

Unification of Chemical and Unification of Chemical and Biological PhasesBiological Phases

Simple Life

Complex Life

Chemical Chemical phasephase

Simple Replicating

System

One continuous process

BiologicalBiological phasephase

Low complexity High complexity

One process – one set of principles

Greater complexity is induced by the drive toward greater DKS


Darwinian ConceptsDarwinian Concepts Chemical ConceptsChemical Concepts natural selectionnatural selection

adaptationadaptation dynamic kinetic dynamic kinetic stability (DKS) stability (DKS)

survival of the fittestsurvival of the fittest drive toward greater drive toward greater DKSDKS

Darwinian concepts firmly rooted in chemistry

A.Pross, J. Syst. Chem. 2011A.Pross, Chem. Eur. J. 2009

Darwinian conceptsDarwinian concepts -- Particular applications Particular applications of broader chemical conceptsof broader chemical concepts

kinetic selectionkinetic selection

fitness fitness

General Theory of EvolutionGeneral Theory of Evolution

Driving force - Driving force - towardtoward greatergreater DKSDKS

MechanismsMechanisms -- complexification complexification (primary) (primary) - - selection selection (secondary)(secondary)


Extended theory embraces both biological and chemical systems

Evolutionary SequenceEvolutionary Sequence

Replication Mutation Selection EvolutionReplication Mutation Selection Evolution

Traditional Darwinian sequenceTraditional Darwinian sequence::

Replication Mutation ComplexificationReplication Mutation ComplexificationNew proposalNew proposal::

SelectionSelection EvolutionEvolution

Martin Nowak (2011): Cooperation – the third evolutionary principle in addition to mutation and selection

“Supercooperators” , 2011

Global Characteristics of Living Global Characteristics of Living SystemsSystems

Extraordinary complexity Extraordinary complexity Dynamic character Dynamic character Far-from-equilibrium stateFar-from-equilibrium state Teleonomy (purposeful nature)Teleonomy (purposeful nature) Homochiral characterHomochiral character DiversityDiversity

Can be understood through the DKS conceptA. Pross, J. Sys. Chem. 2011

Dynamic Kinetic Stability (DKS)Dynamic Kinetic Stability (DKS)

Dynamic Steady States Exist at Dynamic Steady States Exist at Various Levels of ComplexityVarious Levels of Complexity

At cell level At cell level twotwo levels of turnover levels of turnoverProtein degradation and re-synthesisProtein degradation and re-synthesis is a is a tightly regulated process. tightly regulated process. intracellular protein intracellular protein tt1/2 1/2 == 11 mins - 48 hrs 11 mins - 48 hrs Hershko, Ciechanover & RoseHershko, Ciechanover & Rose (Nobel Prize, 2004) (Nobel Prize, 2004)

For molecular replicators there is For molecular replicators there is just just oneone level of turnover level of turnover

At the organismic level At the organismic level threethree levels of levels of turnoverturnover




A: A: In replicative world the stability that In replicative world the stability that counts is counts is dynamic kinetic stability (DKS)dynamic kinetic stability (DKS)..

How can How can highhigh stabilitystability of one kind lead to of one kind lead to low stability low stability of another kind?of another kind?

Q: Q: How could the evolutionary process How could the evolutionary process lead to the formation of lead to the formation of thermodynamically unstable systemsthermodynamically unstable systems??

A Key Step on Road to Complexity - A Key Step on Road to Complexity - Incorporating a Metabolic Capability Incorporating a Metabolic Capability Metabolism = energy gathering capability

Non-Metabolic Metabolic Replicator Replicator

Dynamic Kinetically Dynamic Kinetically Dynamic Dynamic Kinetically Kinetically lessless stable stable moremore stable stable

N. Wagner, A.Pross, E.Tannenbaum, Biosystems, 2010

Metabolism is kinetically selected for

Consequences of MetabolismConsequences 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 lifeThe moment life beganbegan……

Death – reversion to the thermodynamic world




Principle of Natural SelectionPrinciple of Natural Selection

Principle of DivergencePrinciple of Divergence

Darwin’s Two PrinciplesDarwin’s Two Principles

‘Regular’ (thermodynamic) Space

Topology of ‘Regular’ Chemical and Topology of ‘Regular’ Chemical and Replicator SpacesReplicator Spaces

Thermodynamic sink

Replicator (kinetic) Space

ConvergentConvergent DivergentDivergent

Topology of replicator space explains diversity


DKS clarifies Darwin’s Principle of Divergence

Implications of Different Implications of Different TopologiesTopologies

Regular systemsRegular systems:: History History inaccessibleinaccessible

FutureFuture predictablepredictable

ReplicatorsReplicators::History History accessibleaccessible

Future Future unpredictableunpredictable

N. Wagner, A. Pross, Entropy 2011A. Pross, Pure Appl. Chem. 2005

Key ConclusionsKey ConclusionsDKS - 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.

Prof. Emmanuel Tannenbaum – BGUProf. Emmanuel Tannenbaum – BGU Dr. Nathaniel Wagner – BGUDr. Nathaniel Wagner – BGU Dr. Nella Pross - BGUDr. Nella Pross - BGU

AcknowledgementsAcknowledgements

Documents

Toward a General Theory of Evolution