On the origin and evolution of some genetic systems

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

2. 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

3. The major transitions (1995) * * * * * These transitions are regarded to be ‘difficult’

4. 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.)

5. 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)

6. Units of evolution • multiplication • heredity • variation hereditary traits affecting survival and/or reproduction

7. Gánti’s chemoton model (1974) metabolism template copying membrane growth ALL THREE SUBSYSTEMS ARE AUTOCATALYTIC

8. 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

9. Pathways of supersystem evolution metabolism MB boundary MT MBT template BT INFRABIOLOGICAL SYSTEMS

10. 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

11. The formose ‘reaction’ formaldehyde autocatalysis glycolaldehyde Butlerow, 1861

12. 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

13. 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

14. 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

15. 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?

16. Chemical evolution was a race between tar formation and life formation Chemical networks Tar Life What fraction of planets would end up with just tar?

17. Another case: von Kiedrowski’s replicators

18. Von Kiedrowski’s replicator

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

20. Does temperature cycling work?

21. Elongation taxes the system badly

22. Classification of replicators Limited (number of individuals) > (number of types) Unlimited (# of individuals) << (# of types)

23. 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???

24. Simplified error threshold x + y = 1

25. Molecular hypercycle (Eigen, 1971) autocatalysis heterocatalytic aid

26. Parasites in the hypercycle (JMS) short circuit parasite

27. “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

28. …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

29. Hairpin Ribozyme N = 50 39/50 (78%) of the positions were mutated, we used 142 mutants

30. Error rates and the origin of replicators

31. Nature420, 360-363 (2002). Replicase RNA Other RNA

32. 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!

33. Evolving population Error rate Replicase activity • Molecules interact with their neighbours • Have limited diffusion on the surface

34. 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.

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

36. 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!