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Project Progress

Self-Reproducing (EL) Molecular Systems and Darwinian Chemistry (dm)

During the past year Ellington’s Laboratory has focused on filling in several key intermediates in a hypothetical ascent of molecules from simplistic origins to complex catalysts that may have been present in a putative RNA world. Short oligonucleotides may have been generated by prebiotic mechanisms. Some of these oligonucleotides would have been self-replicating. The first step beyond simple, templated self-replication would likely have been the acquisition of catalysis. We have now selected doppelgangers of these early catalysts, simple deoxyribozyme ligases. To enhance our ability to explore sequence space, we have also automated the process for catalyst selection. Catalytic activity need not have been inherent in nucleic acids alone, but would have been likely augmented by cofactors or effectors. Interestingly, it now appears increasingly unlikely that the opposite strategy would have been pursued, that mere binding of a ligand would not have brought about the acquisition of catalytic activity. This finding has additional, important implications for theories of the origin of the genetic code. To demonstrate the ability of nucleic acid catalysts to synergize with molecules in their environment, we have adapted the selected deoxyribozyme ligase to function as an allosteric enzyme, dependent upon ATP for their activity. We have similarly adapted a selected ribozyme ligase to be dependent upon protein and peptide cofactors. Such nucleoprotein enzymes may have stood at the transition between the ancient RNA and modern protein worlds.

In a separate project, we have selected an E. coli strain that completely incorporates an unnatural amino acid throughout its proteome. This â??unColi’ demonstrates that canonical, terrestrial chemistries are adaptable, and serves as an avatar for organisms that may be found on other planets.