Addy Pross

Department of Chemistry, Ben Gurion University of the NegevBe’er Sheva, Israel

HGT & LUCA Conference, The Open University, Milton Keynes, Sept. 4-6, 2013

Seeking the Evolutionary Roots of Horizontal Gene Transfer (HGT)

Biology in Crisis

“Biology today is no more fully understood in principle than physics was a century ago…. the guiding vision has reached its end …. a new, deeper, representation of reality is called for”

Carl Woese

Bottom line: 150 years after Darwin, we still don’t adequately understand biology’s essence and the nature of the evolutionary process

Central HGT & LUCA Questions

How fundamental is HGT to the evolutionary process? What was the nature of LUCA? What does Woese’s ‘Darwinian threshold’ actually

represent? Is the evolutionary process best represented by a tree

or a web? Is HGT Lamarckian or Darwinian?

Regular Chemistry BiologySystems

Chemistry

Systems Chemistry

Systems Biology -‘top-down’ Systems Chemistry -‘bottom-up’Deals with simple replicating chemical systems and the networks they establish

A new area of chemistry

Non-replicative Simple replicative

Complex replicative

G. von Kiedrowski, S. Otto, P. Herdewijn, J. Syst. Chem. 2010

Biology Systems chemistry

To understand how something works, look at a simple version

Simple Life

Complex Life

Biological phase Non-Life

Systems Chemistry:Merging Chemistry and Biology

Chemicalphase

One single physicochemical process

Replication reaction - the underlying connection

A. Pross, J. Syst. Chem. 2011

Darwinian theory?

Molecular Replication

A + B + C + ….. T T Molecular

Replication

Template mechanismS. 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

Replication Reaction is Autocatalytic

79 replication cycles would convert a single molecule to a mole (279 ~ 6. 1023).

a further 83 cycles would generate a mass equal to that of the earth, 1027g!

Replication is unsustainable

Autocatalysis - can exhibit exponential growth

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

StabilityA system is stable if it is persistent, unchanging

over time.

Thermodynamic Stability – an inherent property of a chemical system, one that is quantifiable.

Second Law of Thermodynamics: All systems tend from less stable to more stable

An Alternative Stability Kind

A stability kind associated with replicating systems (chemical or biological) that display persistence

Can underpin a general theory of evolution and help identify the driving force for the evolutionary process

Dynamic Kinetic Stability (DKS)

Pross et al. 2004-2013

Dynamic Kinetic Stability (DKS)

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

A. 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

Replication is unsustainable, therefore for stability rate of replicator formation rate of decay ~=

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

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

Example of Replicator Selection Rule

Qb RNAnucleotides

S. Spiegelman, 1967

(4500 b)Mutant RNA

(220 b)74 replication cycles

Faster RNA drive slower RNA into extinction

In stability terms:

From DK less stable to DK more stable

activated

Replication Mutation Selection Evolution

Sequence of events:

Identifying the Driving Force for Evolution

Simple Life

Complex Life

Simple replicating

entity Drive toward greater DKS

One single physicochemical process

A. Pross, J. Syst. Chem. 2011

Chemicalphase

Biological phase

What actually takes place during evolutionary process?

Chemical (molecular) level:Molecular replicating system simple life

A clear tendency toward complexification during evolution – both chemical and biological

prokaryotes eukaryotes

multicell organisms

Biological level:

ecological networks

Evolutionary Process Characterized by Complexification

Extent of Complexification During Evolution

Simple Life

Complex Life

Chemical phase

Simple Replicating

System

One continuous process

Biological phase

low complexity high complexity

Drive toward greater DKSlow complexity – low stabilityhigh complexity – high stability

A. Pross, J. Syst. Chem. 2011

General Theory of Evolution

A. Pross, J. Syst. Chem. 2011

Extended theory embraces both biological and chemical systems

All stable (persistent) replicating systems will tend to evolve (primarily by complexification) toward systems of greater DKS.

Darwinian Concepts Chemical Concepts

dynamic kinetic stability (DKS)

survival of the fittest drive toward greater DKS Darwinian concepts firmly rooted in chemistry Biology – a complex manifestation of replicative

chemistry

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

Darwinian concepts - Particular applications of broader chemical concepts

kinetic selection

fitness

natural selection

Global Characteristics of Living Systems Explained by DKS

Diversity Functional complexity Dynamic character Far-from-equilibrium state Teleonomy (purposeful nature) Homochiral character

Principle of Natural Selection Principle of Divergence

Darwin’s Two Principles

Origin of DiversityDiversity – a central element of Darwinian theory

- many become few- few become many

‘Regular’ (thermodynamic) Space

Topology of ‘Regular’ Chemical and Replicator Spaces

Thermodynamic sink

Replicator (kinetic) Space

Convergent Divergent

Replicator Space – Open, circumstantial

A. Pross, J. Syst. Chem. 2011Clarifies Darwin’s Principle of Divergence

Topology of replicator space explains diversity

Implications of Different Topologies

Regular systems: History inaccessible

Future predictable

Replicators:History accessible

Future unpredictable

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

Diversification at Chemical Level

nucleotides

(4500 b)Mutant RNA

(220 b)74 replication cycles

activated

1) Replication (VGT) + mutation

Qb RNA

2) HGT – mechanism for diversification that is not directly connected to replication step.

S. Spiegelman et al., PNAS, 1967

HGT already evident at chemical level.

Molecular HGT in Action

N. Lehman et al., Nature 2012 (fig: Attwater & Holliger, Nature 2012)

Cooperative cycle out-replicates individual cycles.An expression of HGT at molecular level!

HGT – not just mechanism for variation but for complexification

Complexification during Evolutionn

Simple Life

Complex Life

Chemical phase

Simple Replicating

System

One continuous process

Biological phase

low complexity high complexity

Drive toward greater DKSlow complexity – low stabilityhigh complexity – high stability

A. Pross, J. Syst. Chem. 2011

Answers to Central HGT QuestionsHow general is HGT in evolution?

HGT crucially important as a major mechanism for diversity and complexification. Operates along the

entire evolutionary process.

Simple replicators – simple HGT molecular level: transformation

More complex replicators – more complex HGT prokaryotic level: conjugation, transduction

eukaryotic level: sexual selectionHGT lesson - variation is not restricted to the replicative step. Nature is opportunistic! Lamarckian character

Nature of LUCAWas LUCA organismal or communal?Is extant life organismal or communal?

Plants cannot fix nitrogen without bacterial assistanceHumans are 90% bacterial by cell countBacteria live in colonies (communicate chemically and coordinate actions eg, in biofilm formation)Animals seem to be individual, but actually network

dependent, replicatively incomplete

Conclusion: life is a network phenomenon, intrinsically communal

Systems Chemistry ViewpointSystems chemistry studies indicate that network formation (complexification) is the primary mechanism for increasing DKS

Central mechanism of abiogenesis would have been network formation.

Conclusion: LUCA was communal because evolution is fundamentally a networking process – right from its origins.

Biology overemphasizes life’s individuality.

Dynamic Kinetic Stability (DKS)

Stability in replicative world (DKS) is not associated with individuals, only with populations. Individual replicators have no DKS.

Individuals don’t evolve, populations do!

Is LUCA a meaningful concept?

Darwinian Threshold = Speciation Threshold

LUCA – diverse population of replicatively coupled entities that preceded speciation

LUCA - associated with Darwinian Threshold

Primal speciation: the point at which replicative networks physically separated, began to utilize available resources differentially, and began to evolve independently

Key ConclusionsDKS - the conceptual bridge between Chemistry and

Biology.

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• Unifies abiogenesis and biological evolution• Integrates Darwinian theory into general chemical

theory• DKS – the driving force for evolution• Systems Chemistry – the road to greater biological

understanding. HGT and LUCA can be better understood by seeking their roots in chemistry

• Scientific reduction in biology is alive and well! Carl Woese’s prophesy of revolution in biology

may be realised - through Systems Chemistry.

Thank you for your attention!