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