Compartmentalization as a prerequisite for the origin of life

Transcription

1 Compartmentalization as a prerequisite for the origin of life Ádám Kun Dpt. Plant Systematics, Ecology and Theoretical Biology, Eötvös University, Budapest, Hungary Evolutionary Systems Research Group Center for Ecological Research, Tihany, Hungary Parmenides Center for the Conceptual Foundations of Science, Munich/Pullach, Germany

2 RNA WORLD We want to understand the development of the RNA world RNA acts as information carrier and as enzymes

3 The Origin of Life Structure and dynamics Structure What can the pieces do? Is it (bio)chemically possible Dynamics How do the pieces fit together? How can they evolve? Á. Kun, A. Szilágyi, B. Könnyű, G. Boza, I. Zachár and E. Szathmáry Annals of the New York Academy of Sciences, 1341,

4 Compartmentalized replicators Compartmentalized replicators (information and metabolism) form proper cells Ribocell = RNA genes in a membrane

5 What about? Useful replicators are those that contribute to the systems (e.g. enzymes) Our best estimate of the minimal gene number is around genes How can so many genes coexist? What about? RNA replicators that accept the benefits of the system, but do not contribute to it

6 Spiegelman s experiment Qβ phage RNA genome and RNA replicase Test tube contains monomer for replication The original 3600 nt long genome is reduced to 550 nt and then to 218 nt Mills et al PNAS 58, ; Kacian et al PNAS 69, ; Saffhill et al JMB 51,

7 The problem of Can enzymes coexist? Will small RNA molecules always overwhelm the system? We study these questions in a compartmentalized experimental and theoretical system Matsumura, S. et al Transient compartmentalization of RNA replicators prevents extinction due to. Science 354(6317):

8 Microfluidics A technique to follow small droplets of water in which reactions can occur. Droplets can be formed, split, fused and selected.

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10 VS Ribozyme and We were familiar the ribozyme There are some true Length (nt) T d (s) r (s -1 ) MDV-VS RNA Parasite Parasite Parasite IV Relativer c a ugaaauug -U- CguAgCAGU U u g acuuuaac GUaUUGUCA C U ug G A U G 700 C-G U A U C-G III A-U C-GA 660 U-A A gcgguaguaagc AgGA A C-G GCU AA 5 GUG-A-CGGuAuUggc g uaagag cguucg-ccc u GAACACGA CAC GAC GUUaUgAcug a a II VI 690 V

11 Three threatments Well-mixed system (bulk) Compartmentalized but not selected Compartmentalized and selected

12 Modelling We follow the number of wild-type ribozyme Mutants in classes according to their replication rates The resource (NTP)

13 Fraction of ribozyme Fraction of ribozyme Modell and experiment Black = experiment Red = modelling a Bulk µ = µ = µ = µ = Unselected, Compartmentalized b c d µ = Selected, Compartmentalized µ = Purge µ = µ = Round Round Round Round Experiment 1 Experiment 2

14 Green fluorescence (replication) Green fluorescence (replication) Green fluorescence (replication) Green fluorescence (replication) Green fluorescence (replication) Round 1 Round 3 Round 5 Round 7 Round 9 e f g Inactive: 4.6% Empty: 62.5% λ = % 8.7% 14.8% 0.2% 93.6% 0.1% 98.9% 0.6% λ = 2.4 λ = 6.2 λ = 6.9 λ = 5.1 Active: 31.3% 68.6% 80.7% 4.9% <0.05% Orange fluorescence (catalytic activity) Inactive: 6.3% Empty: 73.8% λ = % 31.6% 3.5% 26.4% 1.4% 4.6% 1.2% 0.1% λ = 1.2 λ = 1.3 λ = 3.1 λ = 6.9 Active: 19.1% 63.7% 68.3% 92.7% 89.6% Orange fluorescence (catalytic activity) Inactive: 49.5% Empty: 45.3% λ = % 48.1% 3.5% 50.0% 22.8% 54.8% λ = 0.73 λ = 0.69 λ = 0.6 Active: 4.9% 31.7% 44.8% 21.5% Orange fluorescence (catalytic activity) Round 1 Round 2 Round 3 Round 9

15 Paramters Mutational rate Ammount of NTP Occupnacy of the compartments (initial RNA number in the droplets) Error at selection Selection strenght

16 Low and high occupancy Soft and hard

17 Robustness checking modelling Fraction of ribozyme E-6 1E-5 1E-4 1E a b c d λ = 0.6 λ = 7 λ = 0.6 λ = 7 1E-7 1E-6 1E-5 1E-4 1E False negative error rate False positive error rate Selection strength,τ e λ = 0.6 λ = 7 Fraction of ribozyme λ = 0.6 λ = E NTP molecules per droplet (x26,570,800,000) Occupancy (λ)

18 Error Above a critical mutation rate information is lost The phenotypic error is more allowing Individual ribozymes (tested computationally on real ribozyme sequences) can be maintained 1% error. Kun, Á., Mauro, S. and Szathmáry, E Real ribozymes suggest a relaxed error. Nature Genetics 37: Szilágyi, A., Kun, Á., Szathmáry, E Local neutral networks help maintain inaccurately replicating ribozymes. PLoS ONE: e109987

19 Stochastic corrector model Division is random Fitness depends on composition Good composition can form randomly In the original model there was only 2 genes Szathmáry, E. és Demeter, L Group selection of early replicators and the origin of life. J. Theor. Biol. 128( )

20 Stochastic corrector model In an infinite population arbitrary number of genes can coexist Without a 100 gene can coexist in finite population kill the system! Parasite = Uses the resources of the system, but does not contribute to it

21 2nd error Population of cells Independently replicating genes Individual genes can be copied faithfully Redundant gene count Random division of cell (i.e. no control) Each enzyme is essential Hubai AG, Kun Á (2016) Maximal gene number maintainable by stochastic correction The second error. J. Theor. Biol. 405:29 35

22 2nd error Compartmentalization allows for more replicators to coexist (100 is possible). Lack of controlled cell division causes an error like phenomena, in which the increase of information content is not possible because of random division Fraction of viable protocells Log (τ) Log(υ max ) Hubai AG, Kun Á (2016) Maximal gene number maintainable by stochastic correction The second error. J. Theor. Biol. 405:29 35

23 Redundancy helps Fraction of viable ribocells Log (types) Log (ribocell size)

24 2nd error Minimal genomes Riboorganism Replication rates do not need to be equal, but the odd ones out should have a lower activity Or the activity difference should be small (cca. 1%)

25 Chromosomes If the error rate is small enough, then a chromosome (genes strung together) can exist. (1st error is solved) A chromosome solves the second error

26 Summary Transient compartmentalization and selection allows the coexistence of an enzyme and The first error can be overcome by compartmentalizing replicators Compartmentalization of independent replicators leads to the second error do not allow many genes to coexist

27 Acknowledgement Coworkers Prof. Eörs Szathmáry Prof. Mauro Santos Dr. András Szilágyi Dr. Balázs Könnyű Dr. Gergely Boza Dr. István Zachar Dóra Szendrei András Hubai Ádám Radványi Funding ERC (#294332) GINOP NKFI-OTKA K COST action CM1304 THANK YOU FOR YOUR ATTENTION!

28 Matsumura, S. et al Transient compartmentalization of RNA replicators prevents extinction due to. Science 354(6317):