Molecular Mechanisms for the Origin of Life and the RNA World

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This proposal addresses one of the foremost issues in interdisciplinary science research - How did life start? The Earth was formed about four and a half billion years ago, and there is good evidence that life has been present for at least three and half billion years. At some point on the ancient Earth there was a transition from chemistry (simple molecules reacting under the laws of thermodynamics) to biology (complex molecules that control their own replication). The most widely accepted idea for the origin of life is the RNA World hypothesis, which states that RNA, or some kind of nucleic acid polymer very similar to RNA, played an essential role in the origin of life. An RNA strand can act as a template for synthesis of a complementary strand, and for this reason, it can act as a gene that stores information. An RNA strand can also fold to specific three dimensional structures that can act as catalysts that control the rate of chemical reactions. A catalytic RNA is called a ribozyme. Laboratory experiments have developed ribozyme sequences that are able to carry out some of the essential tasks that would be required in a self-replicating RNA system at the time of the origin of life, and these experiments lend support to the RNA World concept. The overall objective of this research program is to develop a comprehensive theory of the way life emerged from a prebiotic chemical mixture and evolved to the stage of single celled organisms. Many of the key issues are conceptual ones that lend themselves to computer simulations and mathematical models. We will design our models so that they have a link to laboratory experiments and to analysis of geological samples. We will address the following questions. Under what conditions can prebiotic chemical reactions generate random sequences of RNA that are long enough to act as ribozymes? How do the specific kinds of polymer used by biology emerge from the diverse mixtures of molecules that we would expect to be generated by chemistry? How did self-replicating ribozymes arise? How did ribozyme systems evolve toward the kind of cellular organisms that we see today? Over the past decade it has become clear that there are many other stars with their own planetary systems; and hence there are many other places in the universe where life could potentially exist. Our work aims to shed light on just how easy or difficult it is for biology to emerge from chemistry on our Earth, and hence how likely it is that we might one day find life on another planet.