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The RNA World Michael T. McManus. Ph.D.. Global overview of all life.

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Presentation on theme: "The RNA World Michael T. McManus. Ph.D.. Global overview of all life."— Presentation transcript:

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. 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. Unfortunately, there are things that behave just as if they has a ‘living’ metabolism, but these things are not alive. BUT!

4 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?

5 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 Mutation Heredity 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 life?

6 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 What is origin of life?*

7 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. Stages of prebiotic evolution

8 Geophysical stage 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 H 2 O, CO, CO 2, N 2, H 2 S and H 2

9 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. 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 CH 4 NH 3 H 2 O H 2 gases 1953: Urey-Miller experiment 1938: Aleksandr Oparin

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

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

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

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

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

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 browse for free at costs about $120, but the 4th edition is worth it! Developmental Biology Sixth Edition Scott F. Gilbert © 2000 Sinauer Associates, Inc., Sunderland, MA

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