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The RNA World Michael T. McManus. Ph.D..

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1 The RNA World Michael T. McManus. Ph.D.

2 Global overview of all life

3 What is life? One way to answer this question would be to require certain properties that we associate with living things. Obviously a bad choice. Many living thing do not have legs. For example: It must have legs It must have metabolism This sounds much more reasonable. BUT! Unfortunately, there are things that behave just as if they has a ‘living’ metabolism, but these things are not alive.

4 What is life? What can be considered to have metabolism but not life?
Fire! Atoms go in, change, and go out. This process is essential for the survival to the phenomenon. The overall phenomenon is constant (i.e. there is a flame) for as long there is food (oxygen, fuel …). There even can be replication (one fire can light another fire). But obviously, we do not consider fire to be alive.

5 What is life? Is there a better way to describe what’s alive?
One could look at the properties that are required for a population to evolve by natural selection. Multiplication Heredity Mutation For individuals of the population, the requirement should be made a bit less strict in that at least the parents fulfill the above requirement (a mule e.g. cannot multiply).

6 What is origin of life?* God? Outer space?
a way to envisage the origin or life as a series of simple steps is more satisfactory than a single, massively improbable event…. *by definition, the origin of life only happened once and no one was around to see it

7 Stages of prebiotic evolution
How did the earth’s crust and atmosphere look like when life originated? Geophysical Stage Chemical Stage Biological Stage Reasonably well understood. How can the building blocks of life (nucleotides, amino acids) be synthesized? These blocks may (partially) have been different from modern blocks. How did the building blocks organize into living organisms? Poorly understood.

8 Geophysical stage H2O, CO, CO2, N2, H2S and H2
The first atmosphere probably consisted of gaseous hydrogen, nitrogen, carbon monoxide and carbon dioxide Gaseous oxygen and water were not thought to be present When the crust cooled the water condensed, rains began, and pools of chemicals began to form

9 Urey-Miller experiment
Chemical stage to vacuum pump boiling water spark discharge liquid water in trap water containing organic compounds water droplets water in condenser electrodes water out CH4 NH3 H2O H2 gases 1938: Aleksandr Oparin 1953: Urey-Miller experiment Experiment by Miller: In a reducing environment, amino acids and bases are easy to synthesize from naturally occurring molecules. The experiments fail in a neutral or oxygen-rich atmosphere.

10 Chemical stage Multiple variations of the study (e.g., atmosphere)
20+ amino acids, sugars, bases for DNA and RNA, ATP, etc. Significance: scenario for the abiotic formation of key carbon polymers (macromolecules) Probable environments Deep sea vents Tidal pools (role of repeated evaporation and concentration – “evapoconcentration”) Chemical events leading to an “RNA World”

11 a word about RNA diversity and catalysis…
Biological stage Some common biopolymers that could have participated in the formation of early life: Proteins: amino acid diversity, catalysis DNA: stability and storage RNA: diversity, storage, and catalysis! a word about RNA diversity and catalysis…

12 RNA structure Hairpin Loops Interior loops Stems Multi-branched loop
Bulge loop Interior loops Multi-branched loop

13 a “natural” RNA enzyme In 1982, Tom Cech et al discovered that an intron within a pre-rRNA from Tetrahymena thermophila can catalyze its own cleavage (called self-splicing) to form the mature rRNA product.

14 RNA structure: a highly evolved “ribozyme”

15 RNA-based RNA polymerase
Why are ribozymes important for an RNA world hypothesis? RNA-based RNA polymerase Hypothetical molecule completely self-replicating + nucleotides

16 reconstructing evolution:making RNA enzymes
SELEX: Systematic evolution of ligands by exponential amplification This technique makes use of large populations of random RNA or DNA sequences as the raw material for the selection of rare functional molecules.

17 RNA enzymes from selex experiments
These types of enzymes have been made! Limited polymerization RNA ligases RNA capping RNA phosphorylation RNA cleavage Peptide bond formation Amide bond formation Can a high school lab do selex experiments? YES!

18 a minimal ribo-organism
Will this be made one day? Bartel and Unrau, TCB 1999

19 overview and conclusions
living cells membrane-bound proto-cells self-replicating system enclosed in a selectively permeable, protective lipid sphere DNA RNA enzymes and other proteins The “Central Dogma” formation of protein–RNA systems, evolution of DNA lipid spheres spontaneous formation of lipids, carbohydrates, amino acids, proteins, nucleotides under abiotic conditions

20 Want to learn more? RNA-specific links!

21 Websites and References
Molecular Biology of the Cell Fourth Edition Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter © 2002 costs about $120, but the 4th edition is worth it! Developmental Biology Sixth Edition Scott F. Gilbert © 2000 Sinauer Associates, Inc., Sunderland, MA browse for free at


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