Exobiology and Evolutionary Biology

PI: Nicholas Hud

Many researchers believe that an early form of life utilized RNA for functions now performed by DNA and proteins. However, the origin of primordial RNA polymers and the process by which they replicated without the aid of protein enzymes remains elusive. It now seems likely that RNA was also preceded by another polymer, one that was more chemically accessible, but one that evolution eventually supplanted with RNA. We have developed a detailed theory of how prebiotic small molecules could have spontaneously formed the first RNA-like polymers. Central to our theory is a molecule, or molecules, that acted as a nanometer-scale surface upon which nucleoside bases stacked in aqueous solution to form Watson-Crick base pairs. We have termed these molecules “molecular midwives”, and envision such molecules as being structurally similar to molecules known
to intercalate the base pairs of contemporary nucleic acids. Stacking interactions with midwives would have initially selected appropriate bases from a diverse solution-phase pool of molecules, organizing these bases into assemblies that facilitated their polymerization into RNA-like structures. Our previous experimental investigations confirm that intercalator-type midwives represent a powerful tool for selectively assembling nucleic acids in template-directed ligation reactions. We now propose to investigate the ability of intercalating molecules to promote mononucleotide polymerization. We also propose to investigate the ability of intercalators to promote the template-directed synthesis of RNA-like polymers with alternative base pairs and backbone linkages. The proposed alternative polymers exhibit properties we believe could have been advantageous for a putative proto-RNA. The successful experimental demonstration of our approach to polymer assembly would provide strong support for the molecular-midwife model of how the first informational polymers of life could have arisen on Earth, and how similar molecular systems might arise in other environments that are of interest to NASA.