![Page 1: On the origin and evolution of some genetic systems](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/1.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/2.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/3.jpg)
The major transitions (1995)
***
*
* These transitions are regarded to be ‘difficult’
![Page 4: On the origin and evolution of some genetic systems](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/4.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/5.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/6.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/7.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/8.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/9.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/10.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/11.jpg)
The formose ‘reaction’
formaldehyde
glycolaldehyde
autocatalysis
Butlerow, 1861
![Page 12: On the origin and evolution of some genetic systems](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/12.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/13.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/14.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/15.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/16.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/17.jpg)
Another case: von Kiedrowski’s replicators
![Page 18: On the origin and evolution of some genetic systems](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/18.jpg)
Von Kiedrowski’s replicator
![Page 19: On the origin and evolution of some genetic systems](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/19.jpg)
• Theory with experiment• J. Mol. Evol., forthcoming
![Page 20: On the origin and evolution of some genetic systems](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/20.jpg)
Does temperature cycling work?
![Page 21: On the origin and evolution of some genetic systems](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/21.jpg)
Elongation taxes the system badly
![Page 22: On the origin and evolution of some genetic systems](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/22.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/23.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/24.jpg)
Simplified error threshold
x + y = 1
![Page 25: On the origin and evolution of some genetic systems](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/25.jpg)
Molecular hypercycle (Eigen, 1971)
autocatalysis
heterocatalytic aid
![Page 26: On the origin and evolution of some genetic systems](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/26.jpg)
Parasites in the hypercycle (JMS)
parasite
short circuit
![Page 27: On the origin and evolution of some genetic systems](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/27.jpg)
“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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/28.jpg)
…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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/29.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/30.jpg)
Error rates and the origin of replicators
![Page 31: On the origin and evolution of some genetic systems](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/31.jpg)
Nature 420, 360-363 (2002).
Replicase RNA
Other RNA
![Page 32: On the origin and evolution of some genetic systems](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/32.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/33.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/34.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/35.jpg)
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](https://reader030.vdocument.in/reader030/viewer/2022032607/56813062550346895d963350/html5/thumbnails/36.jpg)
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!