The RNA World Michael T Mc Manus Ph

The RNA World Michael T. Mc. Manus. Ph. D.

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 H 2 O, CO 2, N 2, H 2 S and H 2 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 CH 4 NH 3 H 2 O H 2 spark discharge gases Experiment by Miller: water out 1938: Aleksandr Oparin 1953: Urey-Miller experiment condenser water in water droplets boiling 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-r. RNA from Tetrahymena thermophila can catalyze its own cleavage (called self-splicing) to form the mature r. RNA product.

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! 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/combin. RNA. htm http: //rnaworld. bio. ukans. edu/class/RNA 00/RNA_World_4. html http: //web. mit. edu/mmcmanus/www/RNAi. html

Websites and References 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 4 th 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. . Show. TOC&rid=dbio. TOC&depth=2