From code to translation - ELTEplantsys.elte.hu/pdf/kunadam/Urbino2016-KunAdam.pdf• Dóra Szendrei...
Transcript of From code to translation - ELTEplantsys.elte.hu/pdf/kunadam/Urbino2016-KunAdam.pdf• Dóra Szendrei...
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
• 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
RNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
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.
Code Biology Conference Urbino 2016
Chapters of the RNA WORLD
• 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
RNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
Code Biology Conference Urbino 2016
Evolution of translation
• How did the RNA world enter the RNA‐peptide world?
• How did translation evolve?
RNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
Code Biology Conference Urbino 2016
Stepwise evolution of translation
• Amino acids –> oligopeptides ‐> translation
• At each step of this series of events fitness need to increase considerably
RNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
Code Biology Conference Urbino 2016
The Genetic Code• Coding linking a triplet to an amino‐acid
• Which are the first amino acids to be included in the code?
RNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
Code Biology Conference Urbino 2016
Empirical and hypothetical abundance of amino acidsRNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
Longo, Liam M., and Michael Blaber. 2012. Protein design at the interface of the pre‐biotic and biotic worlds. Archivesof Biochemistry and Biophysics 526(1):16–21.
Code Biology Conference Urbino 2016
The Genetic Code• Hydrophobic amino‐acids are important!
RNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
U C A GPhe Ser Tyr Cys UPhe Ser Tyr Cys CLeu Ser STOP STOP ALeu Ser STOP Trp GLeu Pro His Arg ULeu Pro His Arg CLeu Pro Gln Arg ALeu Pro Gln Arg GIle Thr Asn Ser UIle Thr Asn Ser CIle Thr Lys Arg AMet Thr Lys Arg GVal Ala Asp Gly UVal Ala Asp Gly CVal Ala Glu Gly AVal Ala Glu Gly G
U
C
A
G
Code Biology Conference Urbino 2016
Catalytic sites of enzymesRNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
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 Codes of Life: The Rules of Macroevolution. Springer, pp. 39‐58
U C A GPhe Ser Tyr Cys UPhe Ser Tyr Cys CLeu Ser STOP STOP ALeu Ser STOP Trp GLeu Pro His Arg ULeu Pro His Arg CLeu Pro Gln Arg ALeu Pro Gln Arg GIle Thr Asn Ser UIle Thr Asn Ser CIle Thr Lys Arg AMet Thr Lys Arg GVal Ala Asp Gly UVal Ala Asp Gly CVal Ala Glu Gly AVal Ala Glu Gly G
U
C
A
GCode Biology Conference Urbino 2016
Catalytic sites of enzymes
• While glycine is involved in catalytic sites, most of the time not alone, and thus do not have catalytic function
RNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
Code Biology Conference Urbino 2016
If not catalysis, then what?• RNA scaffolding• Trans‐membrane regions (transport)• RNA protection / capsid
RNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
Code Biology Conference Urbino 2016
RNA scaffolding
• The amino acids assumed to be the first to enter the code are abundant in the globular part of ribozyme peptides.
RNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
Code Biology Conference Urbino 2016
Trans‐membrane proteins
• RNA can effect the properties of a membrane, but cannot submerge into it without some hydrophobic side chain
RNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
Code Biology Conference Urbino 2016
S layer proteins
• Envelope around archaeal and bacterial cells
• Defense function (among others)
RNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
Code Biology Conference Urbino 2016
Capsid and viral coat protein sequencesRNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
Code Biology Conference Urbino 2016
Capsids and viral coat proteins• 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
RNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
Code Biology Conference Urbino 2016
Supramolecular chemistry• 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
RNA World
Genetic Code
Catalysis
Possible other roles
Supra‐molecular chemistry
Code Biology Conference Urbino 2016
AcknowledgementCoworkers
• 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.