Prebiotic phosphorylation of 2-thiouridine provides either nucleotides or DNA building blocks via photoreduction

• Published in: Nature chemistry 2019-05, Vol.11 (5), p.457-462
• Main Authors: Xu, Jianfeng, Green, Nicholas J., Gibard, Clémentine, Krishnamurthy, Ramanarayanan, Sutherland, John D.
• Format: Article
• Language: English
• Subjects: 631/92/610; 639/638/45/500; 639/638/904; 639/638/92/610; Adenine; Analytical Chemistry; Biochemistry; Biosynthesis; Chemical evolution; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Deoxyadenosine; Deoxyadenosines - chemical synthesis; Deoxyribonucleic acid; DNA; Evolution, Chemical; Gene sequencing; Inorganic Chemistry; Models, Chemical; Nucleotides; Organic Chemistry; Oxidation-Reduction; Phosphorylation; Photochemistry; Photoreduction; Physical Chemistry; Polymers; Prebiotics; Ribonucleic acid; RNA; Thiouridine - analogs & derivatives; Thiouridine - chemical synthesis; Thiouridine - chemistry; Thiouridine - radiation effects; Transcription; Ultraviolet Rays
• ISSN: 1755-4330; 1755-4349
• DOI: 10.1038/s41557-019-0225-x

Breakthroughs in the study of the origin of life have demonstrated how some of the building blocks essential to biology could have been formed under various primordial scenarios, and could therefore have contributed to the chemical evolution of life. Missing building blocks are then sometimes inferred to be products of primitive biosynthesis, which can stretch the limits of plausibility. Here, we demonstrate the synthesis of 2′-deoxy-2-thiouridine, and subsequently 2′-deoxyadenosine and 2-deoxyribose, under prebiotic conditions. 2′-Deoxy-2-thiouridine is produced by photoreduction of 2,2′-anhydro-2-thiouridine, which is in turn formed by phosphorylation of 2-thiouridine—an intermediate of prebiotic RNA synthesis. 2′-Deoxy-2-thiouridine is an effective deoxyribosylating agent and may have functioned as such in either abiotic or proto-enzyme-catalysed pathways to DNA, as demonstrated by its conversion to 2′-deoxyadenosine by reaction with adenine, and 2-deoxyribose by hydrolysis. An alternative prebiotic phosphorylation of 2-thiouridine leads to the formation of its 5′-phosphate, showing that hypotheses in which 2-thiouridine was a key component of early RNA sequences are within the bounds of synthetic credibility. RNA is usually considered to be the first genetic polymer, with DNA a product of a biochemical pathway that arose after the origin of life. Now, studies into the prebiotic phosphorylation of an RNA nucleoside reveal pathways for the synthesis of DNA building blocks, providing experimental support for a prebiotic link between RNA and DNA.