The Center for Chemical Evolution is searching for molecules and reactions responsible for the initial synthesis and evolution of the polymers associated with life. This question poses a number of intellectual and technical challenges. Researchers within the CCE hypothesize that the first biopolymers resembled those known in life today but had unique properties that allowed them to survive, flourish, and evolve on the early Earth. These proto-biopolymers and the environments that fostered their survival define the research themes within the CCE.
The RNA World hypothesis, which suggests early life relied on RNA’s ability to store genetic information as well as perform catalytic functions to exist, is central to many current theories on the evolution of life. Based on plausibly prebiotic conditions, there were likely formidable challenges to the formation of RNA on the early Earth. The Proto-Nucleic Acids theme is considering plausibly prebiotic scenarios resulting in the formation of RNA or a precursor molecule. Studies of the various components (e.g., base, sugar, backbone) have revealed alternatives to the Watson-Crick bases and the phosphodiester backbone that may result in the formation of biopolymers with similar structural and genetic characteristics to extant nucleic acids. The following sections highlight recent discoveries.
The Watson-Crick bases (A, T, G, C) are responsible for storage of genetic information and their base pairing ability contributes to the structural stabilities of DNA and RNA. Alternative nucleobases have been considered in the exploration of possible precursors to extant nucleic acids. By exploring prebiotically plausible heterocycles, CCE researchers discovered 4 molecules that have similar attributes to the Watson-Crick bases: triaminopyrimidine, cyanuric acid, melamine, and barbaturic acid. Previous CCE studies have demonstrated that, at above critical concentrations, pairings of these molecules have a propensity to self-assemble forming gene-length supramolecular structures. When the nucleobases were mixed with ribose, the newly formed nucleoside molecules favored the β-furanose form (found in nature) and still readily formed assemblies. Most recently, the CCE demonstrated that Ribose-5-phosphate mixed with melamine and barbaturic acid form nucleotides in high yields and that the crude mixtures are able to form supramolecular assemblies. Further, the assemblies favored formation of the β-anomers implying a plausible demonstration of selection in the emergence of early bio-polymers.
There were likely only limited quantities of ribose available on the early Earth; CCE research considers alternative backbone chemistries for potentially prebiotic nucleic acids. The thermal instability of mixed-RNA-DNA chimera-duplexes point to the difficulties for the transition (by information transfer) from one homogeneous system (RNA) to another (RNA/DNA) in a prebiotic RNA world. This suggests an alternative scenario of prebiological formation, accumulation and co-evolution of homogeneous systems (RNA and DNA) starting from a heterogeneous mixture of ribo- and deoxyribonucleotides and sequences.
Molecular midwives, small molecules that would enable fragments of nucleic acids to assemble by increasing stability, may have been key in the formation of proto-nucleic acid assemblies. CCE researchers previously explored a number of alternative backbones (Stoop, et al.) that did not readily self-pair or pair with RNA. By using a molecular midwife, like the small molecule proflavin, it was possible to overcome the structural constraints of the alternative sugars and form duplexes.