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.
One of the most enduring mysteries concerning the origin of life is the mechanism by which living systems use homochiral polymers. This homochirality could originate by chemical evolution or biological evolution, or a combination of both. CCE has demonstrated the spontaneous appearance of macroscopic chirality, chiral domain separation and chiral amplification in hydrogen bonded assemblies of achiral nucleobases. We hypothesize that nucleic acid homochirality can be a result of symmetry breaking at the supramolecular polymer level, and homochiral polymers can evolve from domains of supramolecular polymers by facile replacement of one chiral molecule with the preferred one.
How did sugars and bases get together to make the nucleosides of RNA? Many attempts have been made to understand the formation of the nucleosides present in RNA today, but a greater diversity of molecules was certainly present on the early Earth. CCE researchers show that the reactions of sugars and nucleobases likely occurred one of two ways. In monovalent glycosylation, specific conditions or a good leaving group allows a single pair of electrons to form a lasting bond. In divalent glycosylation, two electron pairs allow a nucleobase to add to a sugar more readily. This framework suggests that there is a greater likelihood that noncanonical divalent nucleobases reacted with sugars to form a vast pool of nucleosides on the early Earth, and that it is possible they played an important role in the evolution of nucleic acids.
Biology uses oxygen containing orotidine as the central nucleotide to synthesize the uridine, cytidine and deoxythymidine nucleotides that are the building blocks of RNA and DNA. Switching the oxygen atom on these nucleobases to a sulfur atom produces corresponding thio-nucleosides that are interesting from both a biological/medicinal and origins of life chemistry point of view. Surprisingly, the 2-thioorotidine (a useful plausible prebiotic) counterpart is unstable due to the combined steric and electronic effects and decomposes readily to form ribose. Such a transformation could be useful for producing other nucleosides in the context of chemical evolution on the early Earth.
