Prof. Jack W. Szostak
Title: A primordial RNA alphabet?
Bio:
Dr. Szostak received his B.Sc. from McGill University in Montreal in 1972, and his Ph.D. from Cornell University, Ithaca, NY, in 1977. Dr. Szostak is a University Professor and Professor of Chemistry at the University of Chicago, and an Investigator of the Howard Hughes Medical Institute. Dr. Szostak is a member of the National Academy of Sciences and the American Philosophical Society, and a Fellow of the Royal Society, the American Academy of Arts and Sciences, and the American Association for the Advancement of Science.
During the 1980s Dr. Szostak carried out research on the genetics and biochemistry of DNA recombination, which led to the double-strand-break repair model for meiotic recombination. At the same time Dr. Szostak made fundamental contributions to our understanding of telomere structure and function, and the role of telomere maintenance in preventing cellular senescence. For this work Dr. Szostak shared, with Drs. Elizabeth Blackburn and Carol Greider, the 2006 Albert Lasker Basic Medical Research Award and the 2009 Nobel Prize in Physiology or Medicine.
In the 1990s Dr. Szostak developed in vitro selection as a tool for the isolation of functional RNA, DNA and protein molecules from large pools of random sequences. His laboratory used in vitro selection and directed evolution to isolate and characterize numerous nucleic acid sequences with specific ligand binding and catalytic properties. From 2000 until the present Dr. Szostak’s research interests have focused on the laboratory synthesis of self-replicating systems and the origin of life.
Abstract:
In RNA, the G:C base-pair is much stronger than the A:U base-pair. This results in a strong bias for the incorporation of G and C residues in nonenzymatic RNA template copying chemistry. However, work from the Sutherland group on potentially prebiotic nucleotide synthesis has suggested that the 2-thio pyrimidines were the (prebiotic) precursors of the canonical pyrimidines. We have found that the 2-thio-U:A and 2-thio-C:I base-pairs are isomorphic and isoenergetic. As a result, template copying with an alphabet of 2-thio-U, 2-thio-C, adenosine and inosine shows less bias in nucleotide incorporation, while maintaining good fidelity. The convergence of plausible synthetic pathways with optimal template copying chemistry suggests that modern RNA may have been preceded by a primordial version based on related but distinct nucleotides.
Host: Prof. Jeff Martell