Mosaic nucleic acids that bind purine nucleotides

Abstract

Models for the origin of life have maintained that the first cells relied upon a single biopolymer for both genotype and phenotype. RNA may have provided these activities through its ability to transfer information via base-pairing and its ability to fold into functional structures. It follows that a comprehensive account of abiogenesis would include an understanding of prebiotic ribonucleotide synthesis. However, studies along these lines have shown that, depending on conditions, prebiotic chemistry may yield diverse nucleotides; some of which are based on sugars other than ribose. This monomer pool would likely support the polymerization of nucleic acid molecules characterized by a heterogeneous sugar-phosphate backbone. Copies of such mosaic nucleic acid (MNA) would conserve sequence information, but not the order and content of sugars in the sugar-phosphate backbone. Might MNA represent a possible source of early biological activity? The answer to this question largely depends on whether the structural heterogeneity of the sugar-phosphate backbone would allow for the emergence of selectable function. To test this possibility, we used in vitro selection to isolate purine nucleotide-binding MNA aptamers from a large library of random MNA sequences (containing an ∼1:1 mixed assignment of deoxy- and ribonucleotides). We report two MNA aptamers that bind either ATP or GTP with weak affinity (apparent KDs = ∼350 µM each) and moderate to high specificity. We conclude that variations in nucleic acid backbone content, perhaps introduced by imprecise synthesis, may not have posed an insurmountable barrier for the emergence of simple biological function.