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RNA molecules are thought to have been prominent in the early history of life on Earth because of their ability both to encode genetic information and to exhibit catalytic function. The modern genetic alphabet relies on two sets of complementary base pairs to store genetic information. However, owing to the chemical instability of cytosine, which readily deaminates to uracil, a primitive genetic system composed of the bases A, U, G and C may have been difficult to establish. It has been suggested that the first genetic material instead contained only a single base-pairing unit. Here we show that binary informational macromolecules, containing only two different nucleotide subunits, can act as catalysts. In vitro evolution was used to obtain ligase ribozymes composed of only 2,6-diaminopurine and uracil nucleotides, which catalyse the template-directed joining of two RNA molecules, one bearing a 5'-triphosphate and the other a 3'-hydroxyl. The active conformation of the fastest isolated ribozyme had a catalytic rate that was about 36,000-fold faster than the uncatalysed rate of reaction. This ribozyme is specific for the formation of biologically relevant 3',5'-phosphodiester linkages.

Original publication

DOI

10.1038/nature01185

Type

Journal article

Journal

Nature

Publication Date

19/12/2002

Volume

420

Pages

841 - 844

Keywords

2-Aminopurine, Base Sequence, Binding Sites, Catalysis, Directed Molecular Evolution, Evolution, Molecular, Kinetics, Ligases, Molecular Sequence Data, Nucleic Acid Conformation, Nucleotides, Oligodeoxyribonucleotides, RNA, RNA, Catalytic, Substrate Specificity, Templates, Genetic, Uracil