Transcript Lecture 9 RNA world and emegence of complexity

The RNA World
Michael T. McManus. Ph.D.
Qu ickT ime™ an d a Y UV 420 code c de com pres sor a re ne eded to s ee th is p ictur e.
Global overview of all life
What is life?
One way to answer this question would be to
require certain properties that we associate with
living things.
For example: It must have legs
It must have metabolism
Obviously a bad choice.
Many living thing do not
have legs.
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.
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.
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).
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
Stages of prebiotic evolution
Geophysical Stage
Chemical Stage
Biological Stage
How did the earth’s crust and
atmosphere look like when life
originated?
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?
Reasonably well
understood.
Poorly
understood.
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
Chemical stage
electrodes
to
vacuum
pump
CH4
NH3
H2O
H2
spark
discharge
gases
Experiment by Miller:
water out
1938:
Aleksandr Oparin
1953:
Urey-Miller experiment
condenser
water in
water droplets
boiling water
water containing
organic compounds
liquid water in trap
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.
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”
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…
RNA structure
Hairpin Loops
Interior loops
Stems
Multi-branched loop
Bulge loop
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.
QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.
RNA structure: a highly evolved “ribozyme”
Why are ribozymes important for an RNA world hypothesis?
RNA-based RNA polymerase
• Hypothetical molecule
• completely self-replicating
+ nucleotides
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.
RNA enzymes from selex experiments
These types of enzymes
have been made!
Qui ckTi me™ and a TIFF ( Uncompressed) decompressor are needed to see this pictur e.
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!
a minimal ribo-organism
Will this be made one day?
Bartel and Unrau, TCB 1999
overview and conclusions
living
cells
membrane-bound proto-cells
self-replicating system enclosed in a
selectively permeable, protective lipid sphere
DNA
RNA
formation of
protein–RNA systems,
evolution of DNA
enzymes and
other proteins
formation of
lipid spheres
spontaneous formation of lipids,
carbohydrates, amino acids, proteins,
nucleotides under abiotic conditions
The “Central Dogma”
Want to learn more? RNA-specific links!
http://www.tulane.edu/~biochem/lecture/723/combinRNA.htm
http://rnaworld.bio.ukans.edu/class/RNA/RNA00/RNA_World_4.html
http://web.mit.edu/mmcmanus/www/RNAi.html
Websites and References
http://www.ncbi.nlm.nih.gov/
http://www.ncbi.nlm.nih.gov/Education/index.html
http://www.ncbi.nlm.nih.gov/Class/MLACourse/Glossaries/index.html
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
http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?call=bv.View..ShowTOC&rid=dbio.TOC&depth=2