Exobiology and Evolutionary Biology

PI: M. Reza Ghadiri

Understanding how life arose from non-living matter on Earth or elsewhere in the universe remains a fundamental scientific mystery and a critical goal of the NASA Astrobiology effort. While many origin of life researchers would agree that the emergence of an informational polymer capable of replication and evolution marked the most important stage in the transition from the prebiotic world to biology, the nature of such a polymer remains unclear. The central objective of this proposal is to explore the possibility that reversible chemical transformations resulting in dynamic informational polymers may have played a critical role in the origin of life. We propose to synthesize and characterize two related peptide-based nucleic acid-like oligomers. The proposed oligomers are expected to participate in non-enzymatic template-directed oligomerization, fragment condensation, and self-replication, which were almost certainly fundamental prebiotic processes. The most compelling feature of the proposed structures, however, lies in their capacity for dynamic sequence modification in response to particular environmental cues, stemming from the presence of reversible covalent linkages within the oligomer structures. We hope to demonstrate that dynamic covalent self-assembly could constitute the basis for Darwinian selection and chemical evolution of the potentially prebiotic oligomers. The proposed studies address the fundamental question of how Nature might have bridged the gap between plausible small prebiotic molecules and replicating RNA polymers in an RNA World, and should help establish the characteristics of chemical structures that could have participated in prebiotic evolution. To carry out these studies, we will employ the techniques of synthetic organic chemistry and analyze the proposed oligomers using high-pressure liquid chromatography (HPLC), mass spectrometry, nuclear magnetic resonance spectroscopy (NMR), and array-based sequencing by hybridization.