Transcript The Major Transitions in Evolution

Evolution and the
origin of life
Eörs Szathmáry
München
Collegium Budapest
Eötvös University
Chemical evolution
Units of evolution
1. multiplication
2. heredity
3. variation
hereditary traits affecting
survival and/or
reproduction
Gánti’s chemoton model (1974)
metabolism
template
copying
membrane
growth
ALL THREE SUBSYSTEMS ARE AUTOCATALYTIC
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
Pathways of supersystem evolution
metabolism
MB
boundary
MT
template
BT
MBT
INFRABIOLOGICAL SYSTEMS
What about replication?
• Replication from a chemical point of view
always rests on autocatalysis
• The basic form is
A+X 2A+Y
• very important for biology
• Much more general than DNA
The formose ‘reaction’
formaldehyd
e
autocatalysi
s
glycolaldehyde
Butlerow, 1861
Replication in the formose
reaction
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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
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
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
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?
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?
Another case: von Kiedrowski’s
replicators
Von Kiedrowski’s replicator
Peptide replicator networks
• Theory with experiment
• J. Mol. Evol., forthcoming
Does temperature cycling work?
Elongation taxes the system badly
Classification of replicators
Limited
heredity
Holistic
formose
Modular
Von
Kiedrowski
Unlimited
heredity
genes
Limited
(number of individuals) >
(number of types)
Unlimited
(# of individuals) << (# of types)
A crucial insight: Eigen’s paradox
(1971)
• Early replication must have been errorprone
• Error threshold sets the limit of maximal
genome size to <100 nucleotides
• Not enough for several genes
• Unlinked genes will compete
• Genome collapses
• Resolution???
Simplified error threshold
x+y=1
Molecular hypercycle (Eigen,
1971)
autocatalysis
heterocatalytic
aid
Parasites in the hypercycle (JMS)
short circuit
parasite
“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 wellstirred flow reactor
…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
RNA structure and the error theshold:
Kun, Santos, Szathmáry (2005) Nature
Genetics 37, 1008-1011.
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The 3D shape of the molecule
Enzymatic activity depends on the structure
Phenotype of a ribozyme is the structure
There are fewer structures than sequences
A few mutations in the sequence usually do not
change the structure
• The 2D structure can be computed easily
Hairpin Ribozyme
N = 50
H1
1

H2
10

H3
20

5’ aaacaGAGAAGUcaACCAg
3’
loop A
H4
AAC
A
G
A
A
30

CAC G
|||||
||| u
loop B
AUGGUc CA
GUG u
G
U

UUAUA
50

40
39/50 (78%) of the positions were mutated, we used 142 mutants
Neurospora Varkund Satellite
Ribozyme
IV
690

680

N = 144
V
c
U
a uGaAauuG-U-CguAgCAGU G
||||||||| A
u ||||||||
aCuUuaaC
GUaUUGUCA u G
g

C U710

670
G
U
700
C-G U U A
C-G
III
A-U A
660 C-G
U-A720
730
640
650
740

C-G

 A
A
AA GUG-A-CGGuAuUggc g
A
GCU
gcgguaguaaGc
AgG
5’
|||||| |||
||| |||
|||||||||| u
cguuCg-CcC GAACACGA CAC GACGUUaUgAcug a a



3’ uaagag

780
770
II
760
750
VI
83/144 (57%) of the positions were mutated, we used 183 mutants
Neutral mutions tame the error
threshold
• Extrapolation from the
available mutants as
samples to the whole
fitness landscape
• Accuracy of viral
RNA polymerases
would be sufficient to
run the genome of a
ribo-organism of about
70 genes
Error rates and the origin of
replicators
Nature 420, 360-363 (2002).
Replicase
RNA
Other RNA
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!
Evolving population
Error rate
Replicase
activity
• Molecules interact with their neighbours
• Have limited diffusion on the surface
Toward ribozyme self-replication
Towards a general polymerase
Anabolic autocatalysis I
Anabolic autocatalysis II
Szostak’s vesicles
E - FLUX
Fet Open
Contract n° FP7-225167
Evolvability of molecular systems (analysis of the GARD
model)
The trigger: Doron Lancet’s GARD model
E - FLUX
Fet Open
Contract n° FP7-225167
The mathematical framework for the analysis
GARD dynamics
Eigen equation
Eigen matrix with huge
off-diagonal terms
E - FLUX
Fet Open
Contract n° FP7-225167
Hidden compartmentalization and no selection
Kauffman: Reflexively autocatalytic
protein networks (1986)
Current investigations
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Evolvability is possible only in compartments
Occasionally new autocatalytic loops appear
Can be inherited from one cell to the daugther
Can be selected for, give some evolution
GARD is shadow of protein networks is a shadow
of template replicators
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 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
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!
Open questions
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Origin of efficient replication
Origin of full protocells
Origin of transcription
Origin of highly specific enzymes
Origin of translation