Evolution by Natural Selection and the Origin of Life

1. Evolution by Natural Selection andthe Origin of Life Mauro Santos Universitat Autònoma de Barcelona & Collegium Budapest (Institute for Advanced Study)

2. “There is grandeur in this view of life, with its several powers, having being breathed into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have being, and are being, evolved.” Darwin 1859. The Origin of Species

3. Units of evolution • Multiplication • Heredity • Variation Hereditary traits affecting survival and/or reproduction

4. Origin of life: The genetics- or replication-first approach “At some point a particularly remarkable molecule was formed by accident. We will call it the Replicator. It may not have been the biggest or the most complex molecule around, but it had the extraordinary property of being able to create copies of itself.” Richard Dawkins

5. In actual cells replication means doubling of the DNA (exponential growth), but this requires a quite complicate enzymatic machinery. Earlier replicators had to be far more simple.

6. Replicator-first theorists must explain how such a complicate molecule could have formed before the process of evolution was under way.

7. Origin of life: The metabolism-first scenario “Life, in a deep sense, crystallized as a collective self-reproducing metabolism in a space of possible organic reactions.” Stuart Kauffman

8. Metabolism-first proponents must show that reaction networks capable of growing and evolving could have formed when the earth was young.

9. But what is life? • This may be a philosophical question • Better to ask what a living system is! • Autonomous life is always cellular • But there are several types of cells • The main divide is between eukaryotes (cells with nuclei) and prokaryotes (bacteria)

10. The eukaryotic cell is very complex—too complex! It took 2 billion years for life to reach this complexity!

11. The simplest cells are bacterial • THUS we want to explain the origin of some primitive bacterium-like cell • Even present-day bacteria are far too complex • The main problem is the genetic code

12. DNA first? – Protein first?

13. The RNA world is a nice idea, because… • You do not have to solve the problem of the ORIGIN OF LIFE and that of the ORIGIN OF THE GENETIC CODE at once • In the case of RNA information flows from gene to enzyme and back (lack of translation) • Goes back to Woese (1967), Crick (1968) and Orgel (1968)

14. Early replication is still a problem… • 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???

15. Eigen’s paradox (1971) Suppose that to increase the maintainable amount of information, an evolving (Darwinian) system must acquire a more complex molecular mechanism to reduce the mutation rate. However, to have such a complex molecular mechanism the system must maintain a longer sequence in the first place. The system will encounter a barrier in the evolution of complexity

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

17. Parasites in the hypercycle (Maynard Smith, 1979) short cuts parasite

18. Population structure is necessary! Compartments are, by clonal selection, not only the best countermeasures against molecular parasites, but the best vehicles for the selection of molecular function, such as catalytic aid in metabolism

19. The stochastic corrector model metabolic gene replicase membrane Szathmáry and Demeter (1987) J. Theor. Biol. Zintzaras et al. (2002) J. Theor. Biol. Santos et al. (2003) OLEB

20. Dynamics of the SC model • Independently reassorting genes (with gene redundancy) • 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

22. Robustness to deleterious mutations

25. Microfluidic device to mimic the life cycle of a protocell

26. Microfluidics – Manipulation of droplets

31. RNA secondary structure • There is more structure than sequence • Neutral paths • The phenotype is more easily maintained than the genotype. Phenotypic error threshold which is lower than the genotypic error threshold. Hypothesis: More information can be maintained

32. Peter Schuster 2001. Biol. Chem. 382:1301-1314

33. Neurospora Varkund Satellite Ribozyme N = 144 83/144 (57%) of the positions were mutated, we used 183 mutants

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

36. Maintainable genome size

37. Holmes, E.C. Nat. Genet. News&Views

38. Microfluidics – Manipulation of droplets

41. ‘Lethal’ selfish parasite

42. “I have long regretted that I truckled to public opinion, and used the Pentateuchal term of creation, by which I really meant “appeared” by some wholly unknown process. It is mere rubbish, thinking at present of the origin of life; one might as well think of the origin of matter.” Darwin (letter written in 1863 to J. D. Hooker, the most important British botanist of the nineteenth century). The origin of life, being an event that had occurred in nature, needs to be understood in terms of natural processes.

43. Coauthors Ádám Kun Elias Zintzaras Eörs Szathmáry