Darwinism from Artificial Genomes

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A decade ago, NASA commissioned the National Academy to survey what was known about the limits of life, develop a general theory of life, and suggest ways that alien life might be found in the cosmos. The Academy recommended that synthetic biology be a tool to address such big questions in life science. Synthetic biology goes beyond descriptive biology, which investigates only the one example of life that the natural history on earth has given us. This project implements synthetic biology to examine the plausibility of alternatives to DNA, which is the primary unit of heredity of life on earth. This project also emphasizes a public outreach effort and the training of early career scientists. A novel synthetic chemical system that supports Darwinian evolution will be delivered through this project, which fits the MCB emphasis on "synthetic biology…capturing the power of mechanistic, quantitative, and evolutionary approaches". The "alien" Darwinian biopolymer will have four informational building blocks (PZBS, hypothesized as an optimal number), a polyelectrolyte backbone (hypothesized necessary for Darwinism), and inter-heterocycle hydrogen bonding (hypothesized required for directionality) in the transfer of genetic information as standard GACT DNA does. This will be the first example of a Darwinian system that does not include any natural building blocks. Further, PZBS DNA adds "skinny" and "fat" pairing to Watson-Crick size-complementary pairing, informational structures and functionality unavailable to standard GACT DNA. PZBS DNA will be synthesized chemically and characterized. Polymerases to support PZBS biopolymers amplification will be evolved by compartmentalized self-replication. For sequencing, a transliteration technique to sequence GACTPZ six-letter DNA will be used; creative re-purposing of this will sequence PZBS DNA. PZBS libraries will then be placed under selection pressure to evolve functional PZBS molecules. Crystallography will be applied throughout to advance nucleic acid theory as the PZBS system is advanced.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.