The Origin of Life

Collegium Budapest – Institute for Advanced Study

A Centre for Excellence

But what is life?

This may be a philosophical questionThis may be a philosophical question Better to ask what a Better to ask what a living systemliving system is! is! Autonomous lifeAutonomous life is always cellular is always cellular But there are several types of cellBut there are several types of cell The main divide is between eukaryotes The main divide is between eukaryotes

(cells with nuclei) and prokaryotes (cells with nuclei) and prokaryotes (bacteria)(bacteria)

The eukaryotic cell is very complex—too complex!

The simplest cells are bacterial

THUS we want to explain the origin of some THUS we want to explain the origin of some primitive bacterium-like cellprimitive bacterium-like cell

Even present-day bacteria are far too complexEven present-day bacteria are far too complex The main problem is the genetic codeThe main problem is the genetic code

The major transitions (1995)

Origins of Life in Ravello(last year)

Moderately peaceful coexistence of the Moderately peaceful coexistence of the churcheschurches

The metabolists, the geneticists and the The metabolists, the geneticists and the compartmentalistscompartmentalists

Some synergistic complementationSome synergistic complementation Still not understoodStill not understood

Units of evolution (JMS)

hereditary traits affecting survival and/or reproduction

1. multiplication

2. heredity

3. variation

A crude picture (Deamer)

The prebiotic soup (Oparin—Haldane, Miller) Electric discharge and heatingElectric discharge and heating Strongly reducing atmosphere (water, Strongly reducing atmosphere (water,

methane, ammonia, etc.)methane, ammonia, etc.) No evidence for strong reductionNo evidence for strong reduction Decreased reducing power decreases yieldDecreased reducing power decreases yield Chemical incompatibilityChemical incompatibility

Chemical incompatibility

condition a condition a substance A substance A condition b condition b substance B substance B does NOT imply thatdoes NOT imply that Condition (a+b) is feasible, OR thatCondition (a+b) is feasible, OR that Condition (a+b) Condition (a+b) substances (A+B) substances (A+B) Most formidable example: tar formation Most formidable example: tar formation

We need the (mineral) surface!

Bernal, WBernal, Wächtershäuserächtershäuser Thermodynamic effect: A(bound) + Thermodynamic effect: A(bound) +

B(bound) B(bound) C(bound) + D(leaving) C(bound) + D(leaving) Entropy is on your sideEntropy is on your side Kinetic effect: surface catalysisKinetic effect: surface catalysis Population structure Population structure modifies the modifies the

outcome of natural selectionoutcome of natural selection

Prebiotic pizza (Wächtershäuser)

The formose ‘reaction’

formaldehyde

glycolaldehyde

autocatalysis

Butlerow, 1861

Replication in the formose reaction

Replication is non-informationalReplication is non-informational Autocatalysis – YESAutocatalysis – YES Heredity – NOHeredity – NO Good for metabolismGood for metabolism Not good for geneticsNot good for genetics

The iron-sulphur world

High pressure/high temperatureHigh pressure/high temperature Pyrite surfacePyrite surface Underwater hydrothermal ventsUnderwater hydrothermal vents Reducing power (HReducing power (H22S)S) Pyruvic Pyruvic acid acid (CH(CH33-CO-COOH) -CO-COOH) decomposes at decomposes at

165 C normally, but forms at 250 C under high 165 C normally, but forms at 250 C under high pressure!pressure!

Largely unknown chemistry (astrobiology)Largely unknown chemistry (astrobiology) An ancient reductive citric acid cycle?An ancient reductive citric acid cycle?

Von Kiedrowski’s replicator

SPREAD for replication (von Kiedrowski)

Classification of replicators

Limited Limited heredityheredity

Unlimited Unlimited heredityheredity

HolisticHolistic formoseformose

ModularModular Von Von KiedrowskiKiedrowski

genesgenes

Limited (# of individuals) (# of types)

Umlimited (# of individuals) << (# of types)

Interlude: the RNA world

This idea goes back to Woese, Crick and This idea goes back to Woese, Crick and OrgelOrgel

If ribonucleic acid (RNA) is able to catalyse If ribonucleic acid (RNA) is able to catalyse reactions then we do not need a genetic reactions then we do not need a genetic codecode

Credibility of this idea has been increasing Credibility of this idea has been increasing in the past decadein the past decade

RNA structures in 3 dimensions

Early replication is still a problem (the ‘Holy Grail’)

Small replicators spontaneously undergo Small replicators spontaneously undergo template replicationtemplate replication

Template and copy spontaneously dissociateTemplate and copy spontaneously dissociate Longer replicators stick together: not recursiveLonger replicators stick together: not recursive NonenzymaticNonenzymatic replication is extremely limited replication is extremely limited A selected ribozyme can copy up to 14 A selected ribozyme can copy up to 14

nucleotidesnucleotides That ribozyme is longer than 100 That ribozyme is longer than 100 nt!nt!

Eigen’s paradox (1971)

Early replication must have been error-Early replication must have been error-proneprone

Error threshold sets the limit of maximal Error threshold sets the limit of maximal genome size to <100 nucleotidesgenome size to <100 nucleotides

Not enough for several genesNot enough for several genes Unlinked genes will competeUnlinked genes will compete Genome collapsesGenome collapses Resolution???Resolution???

Molecular hypercycle (Eigen, 1971)

autocatalysis

heterocatalytic aid

Parasites in the hypercycle

parasite

short circuit

Population structure is necessary!

Good-bye to the well-stirred flow reactorGood-bye to the well-stirred flow reactor Adhesion to surface or compartmentationAdhesion to surface or compartmentation Hypercycles (with more than 4 members) Hypercycles (with more than 4 members)

spiral on the surface and resist parasites, spiral on the surface and resist parasites, BUTBUT

Are not resistant to short-circuitsAre not resistant to short-circuits Collapse if the adhesive surface is patchyCollapse if the adhesive surface is patchy Only compartmentation saves Only compartmentation saves themthem

A ‘metabolic’ system on the surface (2000)

A cellular automaton simulation

Reaction: template Reaction: template replicationreplication

Diffusion Diffusion (Toffoli-(Toffoli-MargolusMargolus algorithm) algorithm)

Metabolic Metabolic neighbourhood neighbourhood respectedrespected

Metabolic Replication

Grey sites: neighbourhood

Black: empty site

X: potential mothers

Parasite on metabolism

Parasites do not kill Parasites do not kill the systemthe system

Can be selected for Can be selected for to perform useful to perform useful functionfunction

NatureNature 420,420, 360-363 (2002). 360-363 (2002).

Increase in efficiency

Target and Target and replicase replicase efficiencyefficiency

Copying fidelityCopying fidelity Trade-off among Trade-off among

all three traits: all three traits: worst caseworst case

Evolution of replicases on the rocks

All functions All functions coevolvecoevolve and improve despite and improve despite the tradeoffsthe tradeoffs

Increased diffusion Increased diffusion destroys the systemdestroys the system

‘Stationary’ population

parasites

efficient replicases

Evolving population

Error rate Replicase activity

Compartmentation: a combined model

membrane

replicase

metabolic gene

Bubbles and permeability

We do not know where lipids able to form membranes had come from!!!

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.

Dynamics of the SC model

Independently Independently reassorting reassorting genesgenes Selection for optimal gene composition between Selection for optimal gene composition between

compartmentscompartments Competition among genes within the same Competition among genes within the same

compartmentcompartment Stochasticity in replication and fission generates Stochasticity in replication and fission generates

variation on which natural selection actsvariation on which natural selection acts A stationary compartment population emergesA stationary compartment population emerges

Group selection of early replicators Many more compartments than templates Many more compartments than templates

within any compartmentwithin any compartment No migration (fusion) between No migration (fusion) between

compartmentscompartments Each compartment has only one parentEach compartment has only one parent Group selection is very efficientGroup selection is very efficient Selection for replication synchronySelection for replication synchrony

Principles of the Living State by Tibor Gánti

First Hungarian edition 1971First Hungarian edition 1971 Papers in Papers in BioSystemsBioSystems and JTB and JTB Referenced by othersReferenced by others Oxford University Press edition 2003Oxford University Press edition 2003 Annotated by James Griesemer & E. S.Annotated by James Griesemer & E. S.

Gánti’s chemoton model

metabolismtemplate copying

membrane growth

Something like this we want to synthesize some day

Egalitarian and fraternal transitions (Queller, 1997)

Increase in complexity

“I have been always confused about this but now I’m confused

on a higher plain” (Hamilton)