From code to translation

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From code to translation What could be the role of the first peptides? Ádám Kun & Ádám Radványi Dpt. Plant Systematics, Ecology and Theoretical Biology, Eötvös University, Budapest, Hungary Parmenides Center for the Conceptual Foundations of Science, Munich/Pullach, Germany

RNA WORLD Biology We want to understand the development of the RNA world This is a probable series of events in which cellular organization evolved without peptide enzymes Kun Á., A. Szilágyi, B. Könnyű, G. Boza, I. Zachár and E. Szathmáry 2015. Annals of the New York Academy of Sciences, 1341, 75 95.

Chapters of the RNA WORLD Biology Amino acids were recruited in the genetic code to offer something to the RNA world Peptides synthesis (not template based) was invented to offer something to the RNA world Template based peptide synthesis (translation) was invented to offer something to the RNA world

Evolution of translation How did the RNA world enter the RNApeptide world? How did translation evolve? Biology

Stepwise evolution of translation Amino acids > oligopeptides > translation At each step of this series of events fitness need to increase considerably Biology

The Coding linking a triplet to an amino acid Which are the first amino acids to be included in the code? Biology

Empirical and hypothetical abundance of amino acids Biology Longo, Liam M., and Michael Blaber. 2012. Protein design at the interface of the pre biotic and biotic worlds. Archives of Bio and Biophysics 526(1):16 21.

Hydrophobic amino acids are important! The U C A G U C A G Phe Ser Tyr Cys U Phe Ser Tyr Cys C Leu Ser STOP STOP A Leu Ser STOP Trp G Leu Pro His Arg U Leu Pro His Arg C Leu Pro Gln Arg A Leu Pro Gln Arg G Ile Thr Asn Ser U Ile Thr Asn Ser C Ile Thr Lys Arg A Met Thr Lys Arg G Val Ala Asp Gly U Val Ala Asp Gly C Val Ala Glu Gly A Val Ala Glu Gly G Biology

Biology U C A G Catalytic sites of enzymes U C A G Phe Ser Tyr Cys U Phe Ser Tyr Cys C Leu Ser STOP STOP A Leu Ser STOP Trp G Leu Pro His Arg U Leu Pro His Arg C Leu Pro Gln Arg A Leu Pro Gln Arg G Ile Thr Asn Ser U Ile Thr Asn Ser C Ile Thr Lys Arg A Met Thr Lys Arg G Val Ala Asp Gly U Val Ala Asp Gly C Val Ala Glu Gly A Val Ala Glu Gly G Kun, Á., Pongor, S., Jordán, F. and Szathmáry, E. 2007. Catalytic propensity of amino acids and the origins of the genetic code and proteins. In: M. Barbieri (ed.) The s of Life: The Rules of Macroevolution. Springer, pp. 39 58

Catalytic sites of enzymes Biology While glycine is involved in catalytic sites, most of the time not alone, and thus do not have catalytic function

If not catalysis, then what? RNA scaffolding Trans membrane regions (transport) RNA protection / capsid Biology

RNA scaffolding The amino acids assumed to be the first to enter the code are abundant in the globular part of ribozyme peptides. Biology

Trans membrane proteins Biology RNA can effect the properties of a membrane, but cannot submerge into it without some hydrophobic side chain

S layer proteins Biology Envelope around archaeal and bacterial cells Defense function (among others)

Capsid and viral coat protein sequences Biology

Capsids and viral coat proteins Biology Capsids protect RNA (DNA) They self assemble from numerous copies of one (or more) peptides Protection from the ravages of the environment is important! Capsids are ancient peptides

The first peptides were short, composed of a few amino acids, and were assembled in a non templated manner The genetic code can still be used for the reactions! (there is just no transcription) The properties of di and tripeptides need to be elucidated Biology

Acknowledgement Coworkers Prof. Eörs Szathmáry Dr. András Szilágyi Dr. Balázs Könnyű Dr. Gergely Boza Dr. István Zachar András Hubai Dóra Szendrei Ádám Radványi Funding ERC (#294332) OTKA K100299 Bolyai Fellowship COST action CM1304

THANK YOU FOR YOUR ATTENTION! Kun, Á., et al. 2015. The dynamics of the RNA world: Insights and challenges. Annals of the New York Academy of Sciences. 1341: 75 95.