some open questions for origlife... eörs szathmáry collegium budapest eötvös university münchen
TRANSCRIPT
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Some open questions for Origlife...
Eörs Szathmáry
Collegium Budapest Eötvös University
München
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Units of evolution
hereditary traits affecting survival and/or reproduction
1. multiplication
2. heredity
3. variation
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Gánti’s chemoton model (1974)
ALL THREE SUBSYSTEMS ARE AUTOCATALYTIC
template copying
metabolism
membrane growth
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Pathways of supersystem evolution
boundary
template
metabolism M B
B T
M T M B T
INFRABIOLOGICAL SYSTEMS
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A crucial insight: Eigen’s paradox (1971)
• Early replication must have been error-prone
• Error threshold sets the limit of maximal genome size to <100 nucleotides
• Not enough for several genes• Unlinked genes will compete• Genome collapses• Resolution???
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Simplified error threshold
x + y = 1
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Von Kiedrowski’s replicator
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A more complex chemoton
• Submitted to Plos One• A stochastic
simulation
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A radically new look at the paradox
• Stochastic simulation of the chemoton with two different templare monomers
• Found coexistence of templates that were thought to be competitors
• Dynamical coexistence is sequence-dependent• Carries over to deterministic solutions of the
chemoton, and even to simplifed systems (metabolism and templates in flow reactor)
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Solution of the paradox requires systematic search and insight
• Numerical solutions take a lot of time
• It is important to see how this carries over to long templates
• CERN computing welcome
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The stochastic corrector model for compartmentation
Szathmáry, E. & Demeter L. (1987) Group selection of early replicators and the origin of life. J. theor Biol. 128, 463-486.
Grey, D., Hutson, V. & Szathmáry, E. (1995) A re-examination of the stochastic corrector model. Proc. R. Soc. Lond. B 262, 29-35.
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Dynamics of the SC model
• Independently reassorting genes• Selection for optimal gene composition between
compartments• Competition among genes within the same
compartment• Stochasticity in replication and fission generates
variation on which natural selection acts• A stationary compartment population emerges
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What is the limit of genome size in the SCM?
• It is about a dozen unlinked genes
• Selection for chromosomes
• Requires evolutionary increase in replication accuracy
• Calls for evolution of better-than-random segregation mechanisms
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This is surprisingly linked to the origin of enzyme specificity
• Imagine a pathway to be enzymatized
• Is there selection from a few, inefficient, multifunctional enzymes to many, efficient, highly specific enzymes (Kacser question)
• The answer is negative in the SCM due to the assortment load (if one gene is lacking, others can do the work)
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Chromosomes favour metabolic evolution
• Because genes are not lost due to reassortment
• Highly specific enzymes evolve
• If there selection againts side reactions!
• Further work needed with better chemical model
• To be submitted soon
• Requires CERN resources
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The origin of metabolism
• Is a hard question
• Coevolution with other subsystems is likely
• One can generate some pre-insights, but this does not replace detailed simulations
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The problems of phylogenetic reconstruction (top-down)
• LUCA was too advanced • Reconstructions (e.g. Delaye et al. OLEB in press)
cannot reach deep enough• The fact that metabolic enzymes are not well
conserved does not mean that they were not there!• Scaffolds (pre-RNA, primitive metabolic
reactions) may have disappeared without leaving a trace behind!!!
• A more synthetic approach is needed• General evolutionary mechanisms must be sought
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Two contrasting modes of enzymatic pathway evolution
Horowitz (1945) : retroevolution• Ancient non-enzymatic pathway:• A B C D• Progressive depletion of D, then C, then B, then A• Selection pressure for enzyme appearance in this order• Homologous enzymes will have different mechanisms
Jensen (1976) enzyme recruitment (patchwork)• One possible mechanism: ambiguity and progressive
evolution of specificity• Homologous enzymes will have related mechanisms• Enzyme recruitment from anywhere (opportunism)
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The two views are not necessarily in contradiction
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Some elementary considerations
O L
Environment 1 Environment 2
Organic synthesis
Life
•Autotrophy impossible
•Enzymatic pathways are likely to be radically new inventions
L
O
•Autotrophy possible
•Enzymatic pathways may resemble non-enzymatic ones
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Further complication of supersystem organization
• The example of the Template/Boundary system: progressive distinction from the environment
Metabolites pass freely Metabolites are hindered
evolution
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Evolution of metabolism: primitive heterotrophy with pathway innovation
A
B
C
D
Necessarily heterotrophic protocell
ABC
D
A
B
C
ABC
D
Evolved enzymatic reaction
Assume D is the most complex
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Evolution of metabolism: primitive autotrophy with pathway retention
A
B
C
D
A
B
C
D
a
b
c
d
a
b
c
DRetroevolution is also likely because of membrane coevolution
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Progressive sequestration
• Initially only templates are kept in• They can evolve catalytic properties• Carriers and channels can also evolve• Membrane permeability can become progressively
restrictive• Finally, only a very limited sample of molecules
can come in• Inner and outer environments differentiate• Membrane and metabolism coevolve gradually
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All these ingredients (and more) must be put together
• Supersystem evolution
• Changing environments
• Progressive sequestration
• Duplication and divergence of enzymes
• Selection for cell fitness
• Network complexification
• The platform by Christoph Flamm
• Computational resources of CERN!