2001 Annual Science Report
Scripps Research Institute Reporting | JUL 2000 – JUN 2001
Self-Reproducing (EL) Molecular Systems and Darwinian Chemistry - Ellington's Laboratory
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.
PROJECT MEMBERS:Andrew Ellington
RELATED OBJECTIVES:Objective 2.0
Develop and test plausible pathways by which ancient counterparts of membrane systems, proteins and nucleic acids were synthesized from simpler precursors and assembled into protocells.
Replicating, catalytic systems capable of evolution, and construct laboratory models of metabolism in primitive living systems.
Expand and interpret the genomic database of a select group of key microorganisms in order to reveal the history and dynamics of evolution.
Search for evidence of ancient climates, extinct life and potential habitats for extant life on Mars.
Determine the presence of life's chemical precursors and potential habitats for life in the outer solar system.
Understand the human-directed processes by which life can migrate from one world to another.