On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös...

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On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University

Transcript of On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös...

Page 1: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

On the origin and evolution of some genetic systems

Eörs Szathmáry

Collegium Budapest AND Eötvös University

Page 2: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

John Maynard Smith (1920-2004)

• Educated in Eaton• The influence of J.B.S.

Haldane• Aeroplane engineer• Sequence space• Evolution of sex• Game theory• Animal signalling• Balsan, Kyoto,

Crafoord prizes

Page 3: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

The major transitions (1995)

***

*

* These transitions are regarded to be ‘difficult’

Page 4: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Difficulty of a transition

• Selection limited (special environment)

• Pre-emption: first come selective overkill

• Variation-limited: improbable series of rare variations (genetic code, eukaryotic nucleocytoplasm, etc.)

Page 5: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Difficult transitions are ‘unique’

• Operational definition: all organisms sharing the trait go back to a common ancestor after the transition

• These unique transitions are usually irreversible (no cell without a genetic code, no bacterium derived from a eukaryote can be found today)

Page 6: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Units of evolution

hereditary traits affecting survival and/or reproduction

1. multiplication

2. heredity

3. variation

Page 7: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Gánti’s chemoton model (1974)

ALL THREE SUBSYSTEMS ARE AUTOCATALYTIC

template copying

metabolism

membrane growth

Page 8: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

The latest edition: OUP 2003

• After several editions in Hungarian

• Two previous books (the Principles and Contra Crick) plus one essay

• Essays appreciating the biological and philosophical importance

Page 9: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Pathways of supersystem evolution

boundary

template

metabolism M B

B T

M T M B T

INFRABIOLOGICAL SYSTEMS

Page 10: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

What about replication?

• Replication from a chemical point of view always rests on autocatalysis

• The basic form is

A + X 2 A + Y

• very important for biology

• Much more general than DNA

Page 11: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

The formose ‘reaction’

formaldehyde

glycolaldehyde

autocatalysis

Butlerow, 1861

Page 12: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Replication in the formose reaction

• Replication is non-informational• Autocatalysis – YES• Heredity – NO• Good for metabolism• Not good for genetics• Butlerow was born on the 15th Sept, 1829• He was regarded as one of the best lecturers of his

time. His lectures were lucid and thorough, yet his language was colourful. Local society often preferred his lectures to the theatre

Page 13: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Primitive ancestry of the reverse citric acid cycle

• Was proposed by Günter Wächtershäuser (1990)

• Coupled to CO2 fixation and pyrite formation around deep-sea hydrothermal vents

Page 14: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

The main problem of the origin of life is metabolite channelling

• Enzymes speed up reactions relative to the unwanted reactions

• Spontaneous decay reactions abound

• Maintenance, not only reproduction, requires autocatalysis

dx/ dt = k x – d x = 0

Page 15: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

All network models neglecting side reactions are seriously incomplete

• E.g. protein networks

• In model assumptions, a reaction is either good or neutral for the system – but the number of harmful transformations is in fact much higher

• Did life emerge from a chemical canyon?

Page 16: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Chemical evolution was a race between tar formation and life

formation

Chemical networks

Life Tar

What fraction of planets would end up with just tar?

Page 17: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Another case: von Kiedrowski’s replicators

Page 18: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Von Kiedrowski’s replicator

Page 19: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

• Theory with experiment• J. Mol. Evol., forthcoming

Page 20: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Does temperature cycling work?

Page 21: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Elongation taxes the system badly

Page 22: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Classification of replicators

Limited heredity

Unlimited heredity

Holistic formose

Modular Von Kiedrowski

genes

Limited (number of individuals) > (number of types)

Unlimited (# of individuals) << (# of types)

Page 23: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

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???

Page 24: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Simplified error threshold

x + y = 1

Page 25: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Molecular hypercycle (Eigen, 1971)

autocatalysis

heterocatalytic aid

Page 26: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Parasites in the hypercycle (JMS)

parasite

short circuit

Page 27: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

“Hypercyles spring to life”…

• Cellular automaton simulation on a 2D surface

• Reaction-diffusion

• Emergence of mesoscopic structure

• Conducive to resistance against parasites

• Good-bye to the well-stirred flow reactor

Page 28: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

…but then die if modelled in more detail

• Are not resistant to short-circuits

• Collapse if the adhesive surface is patchy (the mesoscopic structure collapses)

• Only compartmentation saves them

Page 29: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Hairpin Ribozyme

aaacaGAGAAGUcaACCAg|||||

A G AA

AUGGUcCAUUAUAUG

A C A

GUG

CACG|||

uu

1

10

20 30

40

50

5’

3’

H1

loop A

H2 H3 H4

loop BaaacaGAGAAGUcaACCAg

|||||A G A

A

AUGGUcCAUUAUAUG

A C A

GUG

CACG|||

uu

1

10

20 30

40

50

5’

3’

H1

loop A

H2 H3 H4

loop B

N = 50

39/50 (78%) of the positions were mutated, we used 142 mutants

Page 30: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Error rates and the origin of replicators

Page 31: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Nature 420, 360-363 (2002).

Replicase RNA

Other RNA

Page 32: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Increase in efficiency• Target efficiency:

the acceptance of help

• Replicase efficiency: how much help it gives

• Copying fidelity

• Trade-off among all three traits: worst case

The dynamics becomes interesting on the rocks!

Page 33: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Evolving population

• Molecules interact with their neighbours• Have limited diffusion on the surface

Error rate Replicase activity

Page 34: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

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.

Page 35: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

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

Page 36: On the origin and evolution of some genetic systems Eörs Szathmáry Collegium Budapest AND Eötvös University.

Group selection of early replicators

• Many more compartments than templates within any compartment

• No migration (fusion) between compartments

• Each compartment has only one parent• Group selection is very efficient• Selection for replication synchrony Chromosomes!