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Darwinian Evolution of RNA Molecules In Vitro

"The First...Evolutionary Adaptation in a Molecular Genetic System."
Nov 16, 2009 Don Kaiser

Evolution of an RNA World The Gutell Lab, The University of Texas at Austin

Scripps Research Institute scientists have devised and patented a simple microfluidic chamber that may hold the answer to the mystery of the creation of life on earth. Life as we know it today synthesizes proteins (polymers of amino acids) using instructions encoded by cellular genes (polymers of deoxyribonucleic acid or DNA). Present-day protein synthesis also requires intermediary ribonucleic acid (RNA) polymers. Evolutionary biologists have generally hypothesized that one of these three polymers was the original bio-polymer of the first forms of life. One possibility is that genes came first and then proteins. Another possibility is that proteins came first and then genes. However, because genes are required to make proteins, and proteins are required to make genes, the problem of considering which came first is like that of the chicken or the egg.

An RNA World
Because DNA and proteins are so intimately related and co-dependent on one another, many scientists consider it unlikely that either arose independently. Thus, a more credible candidate for the primordial polymer of life is the intermediary RNA. The idea was apparently first suggested by Francis Crick who shared the Nobel prize with James Watson for discovering the structural basis for the storage of genetic information by nucleic acids. RNA is a reasonable candidate because it has the DNA-like properties of information storage and replication and the catalytic properties of some proteins. Additionally, RNA's intermediary position in protein synthesis, allows for the development of the current life paradigm (DNA-RNA-protein) and avoids the chicken or the egg dilemma. Crick and others favored the so-called RNA World hypothesis even before the catalytic properties of RNA were known.

Self-Sustained Molecular Replication

The possibility that the first life on earth was RNA-based is now even more credible following recently published studies by scientists at the Scripps Research Institute in La Jolla, California. One study in

particular demonstrates self-sustained replication of unique artificial RNA enzymes consisting of two separate components (each about 70 nucleotides in length) that catalyze each other's synthesis in vitro. Starting with a various assortment of such molecules, scientist Tracey Lincoln took advantage of their rapid replication times (approximately 1 hour), occasional genetic changes (recombinations), and her own imposed environmental changes to observe true Darwinian evolution in vitro.

Survival of the Fittest Molecules

After many replication cycles, new structural changes were identified in the predominant population of molecules. In similar experiments published by Sarah Voytek, the mutant molecules were biochemically characterized and shown to have acquired new functions that were likely responsible for their adaptation to, and natural selection in, the changed environment. Referring to Lincoln's experiments, principle investigator Gerald Joyce exclaimed, "This is the first example, outside of biology, of evolutionary adaptation in a molecular genetic system." The entire self-sustained evolutionary process was carried out in the absence of any proteins, DNA, lipids, or other biological materials.

Future RNA World Applications

Tremendous practical applications are possible based on these kinds of studies. One application is the ligand-dependent amplification of molecules. Unique self-replicating molecules that require binding to some other molecule (ligand) in order to replicate can be used to identify or determine the concentration of those ligands. Observing amplification indicates that the ligand is bound. Thus, these molecules can be used as sensitive molecular sensors for the ligands which could be toxins, environmental factors, or other important molecules. Another application is the utilization of the evolutionary process to optimize the binding of certain selfreplicating molecules to their ligands. Such a system could be used to develop new drugs. In nature, the evolutionary process has designed the best and highest affinity ligands known to exist (such as certain toxins and receptors). Therefore, taking advantage of this process in vitro to design new drugs with optimal binding characteristics holds enormous potential. Scripps scientists have patented microfluidic devices suitable for the research and development of such applications.

Read on

Darwin, Evolution & Selection Nucleotides and Nucleic Acids DNA & RNA What is Ribonucleic Acid or RNA?

Creation of Life
RNA and even catalytic RNA (ribozymes), are normally considered to be ordinary inanimate organic molecules. By demonstrating their self-sustained replication and Darwinian evolution, the Scripps scientists have raised the possibility that these simple molecules have crossed over into the realm of the living.

Sources
Joyce, Gerald F., Evolution in an RNA World, Cold Spring Harb Symp Quant Biol sqb.2009.74.004, DOI:10.1101/sqb.2009.74.004, 08/10/2009. Lincoln, Tracey A. and Gerald F. Joyce, Self-Sustained Replication of an RNA Enzyme, Science, vol. 323. no. 5918, pp. 1229-1232 (2009), DOI: 10.1126/science.1167856, 01/08/2009. Voytek, Sarah B. and Gerald F. Joyce, Niche partitioning in the coevolution of 2 distinct RNA enzymes, PNAS May 12, 2009, vol. 106, no. 19, 7780-7785, DOI: 10.1073/pnas.0903397106, 04/29/2009. Lam, Bianca J and Gerald F. Joyce, Autocatalytic aptazymes enable ligand-dependent exponential amplification of RNA, Nature Biotechnology 27, 288-292 (2009), DOI:10.1038/nbt.1528, 02/22/2009. Paegel, Brian M. and Gerald F. Joyce, Darwinian evolution on a chip, PLoS Biology 6(4):e85, ISSN: 1545-7885, DOI:10.1371/journal.pbio.0060085, 01/05/2008.

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