Transcript On the Emergence of Biological Complexity:

Toward a General Theory of Evolution
Addy Pross
Department of Chemistry, Ben Gurion University
Be’er Sheva, Israel
ILASOL - Dcember 25, 2011
Chemistry-Biology Interface
Problematic
Still struggling to answer central life questions
What is
life?
How did
life
emerge?
How to
make
life?
General Theory of Evolution
Attempts to extend and reformulate Darwinian
thinking in chemical terms to help bridge
between biological and 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)
Molecular Replication
A + B + C + …..
T
T
Molecular
Replication
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
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 generate a mass
equal to that of the earth, 1027g!
Replication is unsustainable
T. Malthus, An Essay on the Principle of Population, 1798
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
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
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
Less Stable
Thermodynamically
More Stable
Replicator World:
Dynamic kinetically
Less Stable
Dynamic kinetically
More Stable
A. Pross, J. Syst. Chem. 2011
A. Pross, Pure Appl. Chem. 2005
How Did Life Emerge?
Inanimate
matter
Chemical
Phase
?
Biological
Phase
Simple
Complex
Life Darwinian Life
theory
One single physicochemical process
initiated by simple replicating entity
Process defined by drive toward greater DKS
A. Pross, J. Syst. Chem. 2011
Evidence for Single Process
Both chemical and biological phases
exhibit similar underlying patterns
(1) The essence of biology:
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
(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
Complexification Enhances
RNA Replication
Autocatalysis
A +B
T
T
Cross-catalysis
A + B
A’ + B’
E’
E
E
E’
Slow replication,
limited exponential
growth
Fast replication,
self-sustained
exponential growth
Complexification enhances replicating ability at
the molecular level!
G.F. Joyce, T.A. Lincoln, Science, 2009
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.
Unification of Chemical and
Biological Phases
Chemical
Biological
Simple
Simple
Complex
phase
phase
Replicating
Life
Life
System 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
Darwinian concepts - Particular applications
of broader chemical concepts
Darwinian Concepts
natural selection
adaptation
fitness
survival of the fittest
Chemical Concepts
kinetic selection
dynamic kinetic
stability (DKS)
drive toward greater
DKS
Darwinian concepts firmly rooted in chemistry
A.Pross, J. Syst. Chem. 2011
A.Pross, Chem. Eur. J. 2009
General Theory of Evolution
 Driving force - toward greater DKS
 Mechanisms - complexification (primary)
- selection (secondary)
Extended theory embraces both biological and
chemical systems
A. Pross, J. Syst. Chem. 2011
Evolutionary Sequence
Traditional Darwinian sequence:
Replication
Mutation
New proposal:
Replication
Mutation
Selection
Evolution
Selection
Evolution
Complexification
Martin Nowak (2011):
Cooperation – the third evolutionary principle in
addition to mutation and selection
“Supercooperators” , 2011
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
Dynamic Kinetic Stability (DKS)
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 hrs
Hershko, Ciechanover & Rose (Nobel Prize, 2004)
 At the organismic level three levels of
turnover
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
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 high stability of one kind lead to
low stability of another kind?
A Key Step on Road to Complexity Incorporating a Metabolic Capability
Metabolism = energy gathering capability
Non-Metabolic
Replicator
Dynamic Kinetically
less stable
Metabolic
Replicator
Dynamic Kinetically
more stable
Metabolism is kinetically selected for
N. Wagner, A.Pross, E.Tannenbaum, Biosystems, 2010
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
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
Darwin’s Two Principles
Principle of Natural Selection
Principle of Divergence
Topology of ‘Regular’ Chemical and
Replicator Spaces
Thermodynamic
sink
‘Regular’ (thermodynamic)
Space
Convergent
Replicator (kinetic)
Space
Divergent
Topology of replicator space explains diversity
DKS clarifies Darwin’s Principle of Divergence
A. Pross, J. Syst. Chem. 2011
Implications of Different
Topologies
Regular systems:
History inaccessible
Future predictable
Replicators:
History accessible
Future unpredictable
N. Wagner, A. Pross, Entropy 2011
A. Pross, Pure Appl. Chem. 2005
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
30
reaction.
Acknowledgements
Prof. Emmanuel Tannenbaum – BGU
Dr. Nathaniel Wagner – BGU
Dr. Nella Pross - BGU