Looking for the Cradle of Life

Sergio BranciamoreDBAG- University of Florence - Italy

Origin of Life: a multidisciplinary

problem

Chemicalapproach

Biologicalapproach

Theoreticalapproach

Erwin Schrödinger

“What is Life ?”, 1944

“What is Life today ?”

Pathways of supersystem evolution

boundary

template

metabolism M B

B T

M T M B T

INFRABIOLOGICAL SYSTEMS

The Transition from the RNA to the DNA World

The recipe of rising life1. Synthesis and accumulation of precursors

(nucleotides)

2. Joining of precursors into larger molecules

3. Protection of biomolecules from degradation

4. Expression of “biological” potentiality of the informational molecules

Classical research: Aqueous Solution Chemistry (primordial oceans)

A.I. Oparin (~1920) - J.B.S. Haldane (~1930)

““The Primordial Soup”The Primordial Soup”

S.L. Miller (1953)

Main problems of prebiotic chemistry in aqueous solution:

Dilution: concentration of reactants

Building blocks synthesis

Polymerization:

( ) ( 1) 2n M n MM P P H O ( ) ( 1) 2n M n MM P P H O

Hydrolysis and not polymerization occurs !!

H2 O

H2 O

H 2O H

2O

H 2O H

2O

H 2O H

2O

H 2O

H 2O

H 2O

H2O

H 2O

H2O

H2O

H2O

H2 O

H 2O

H2O

H 2O H

2O

H 2O H

2O

H 2O H

2O

H 2O

H 2O

H2O

H 2O

H2O

H2O

H2O

( ) ( 1) 2n M n MM P P H O

Main problems of prebiotic chemistry in aqueous solution:

Dilution: concentration of reactants

Building blocks synthesis

Polymerization:

Hydrolysis and not polymerization occurs !!

Polymers eventually formed are very susceptible to degradation (environmental persistence)

Looking for theSuitable Environment

for the Emergence of Life

Possible Physical Settings

The snowball hypothesis(L.E. Orgel, A.V. Vlassov)

Hydrothermal vent & pyrite

(G. Wächtershäuser M.J. Russel )

Mineral environment

It is necessary a protected confined environment where the primordial genetic

molecule, could originate and express its biological potential to self-replicate

and evolve

The “Mineral Honeycomb”

“. . . clays and other minerals were necessary to:

1) Concentrate the organics present in a dilute ocean by adsorption;

2) Protect these organics from destruction by U.V. light;

3) Catalyze the polymerization of adsorbed organics . . . ”

J.D. Bernal (1951)

The mechanism of accumulation is driven by heat in a twofold way. Thermal convection shuttles the molecules vertically up and down and thermophoresis pushes the molecules horizontally to the right. The result is a strong molecular accumulation from the top to the bottom (linear concentration color scale).

Heat-driven molecular accumulation in hydrothermal pores.

Section through aragonite (CaCO3) from the submarine hydrothermal vent field at Lost City

Formation of sugar-phosphates in the presence of mineral particles, Pitsch et al., OLEB (1995)

Stabilization of ribose in the presence of borate

minerals, Ricardo et al., Science (2004)

Synthesis of Nucleobases by Formamide in the

Presence of Montmorillonite, Saladino et al.,

ChemBioChem (2004)

Synthesis of building blocks

\

Montmorillonite catalyzes the formation of oligonucleotides up to 50-mer long

Ertem and Ferris Nature (1996)

Ferris et al. Nature (1996)

A CT G

TCC

Polymerization of precursors into larger molecules

Protection & Expressionof Nucleic Acids

Adsorbed on Minerals

RNA-Clay Complexes

minerals

ssRNAViroid

HairpinRibozyme

RNA-mineralComplexes

16S RNA

Hammerhead Ribozymes

Hairpin Ribozymes

Viroids

Structural characteristics:– Single stranded, circular, 250-400 nt long– Mostly, self-complementary (double helix)– Not coding– “Nude” (without capside)– Replication by rolling circle– Smallest and simplest autonomous infective agents

Viroids Could be Relics of the RNA World

Cleavage Site

U AU AC GU AC GC GA UAAGC

GUA

AU

GC

GC

U

GC

GCG

C

53 3925’3’

AG

AU

CG

II

III

CCG

IAGU

C

ACAG

U A

GU A

GC UC

AAA

HAMMERHEAD

U AU AC GU AC GC GA UAAGC

GUA

AU

GC

GC

U

GC

GCG

C

53 3925’3’

AG

AU

CG

II

III

CCG

IA

GUC

ACAG

U A

GU A

GCUC

AAA

Cleavage Site

HAMMERHEAD

Interactions of Hammerhead and Hairpin Ribozymes with Clay Particles

Increase self-cleavage kinetics of ribozymes (“natural prebiotic chaperon”);

Protect RNA from degradation.

0 50 100 150 200 2500

10

20

30

40

50

60

70

Time

% s

elf-cl

eava

ge

+ montmorillonite

Kobs= 0.343 min-1

F∞= 0.58

free solution

Kobs= 0.027 min-1

F∞= 0.55

UV irradiation of ADHR1 hairpin ribozymes in the presence of Montmorillonite

UV254 nm

Self-cleavage

The UV inactivation of hairpin ribozyme is strongly reduced by the presence of clay minerals

Early replication is still a problem: Eigen’s paradox (1971)

• Early replication must have been error-prone

Quasispecie

Error catastrophe

No genome without enzymes, and no enzyme without genomes

Eigen’s paradox

Early replication is still a problem: 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???

R1R2

R3

R4

R5

HYPERCYCLE MODEL

R6

autocatalysis

heterocatalytic aid

short circuit

parasite

Population structure is necessary!

Good-bye to the well-stirred flow reactor !!!

The evolutionary processes need adhesion to

surface or compartmentation

The stochastic corrector model

Hypercycle in a (mineral) surface

Hypercycles (with more than 4 members) spiral on the surface and resist to some type of parasites

Metabolism

R1

R4 R2

R3

The metabolic model

nn

ii

iii

xM

Mkxdt

dx

/1

1

)(

)()(

x

xx

SEM image of etch-pit network near the surface of a weathered Shap alkali feldspar. (Scale bar 20 µm.)

ribozymes

resources

nucleotidesmetabolism

Pore

Mineral environment

Evolution of an RNA population in a network of inorganic compartments

Phosphate (from apatite)

N-Base

Ribose

RADIATION

ProtectionInteraction Evolution

Conclusions

The formation of a “close” association between prebiotic genetic molecules – whatever they were – and mineral surfaces could have represented a crucial step in the origin, persistence and activity of genetic material in primeval terrestrial habitats, opening the way to the biochemical evolution on Earth suggesting the possibility of a…..Mineral-Mediated Life

RollingCircle

Replicative cycle

5’ OH

2’

P

3’

5’ OH

2’

P

3’

InfectiveViroid