Building the Building Blocks RNA Nucleotides

A productive hypothesis, which has stimulated the design of laboratory experiments that might mimic the formation of biochemical compounds on early Earth, has been the notion that ribonucleic acid (RNA) was the primordial genetic material. Many scientists believe that RNA arose before DNA, and that DNA later took over the information-storage role from RNA. Among the reasons for this view are the modern routes by which pieces of DNA are made. For example, the characteristic sugar that forms the backbone is generated by an enzyme that removes an oxygen (the "deoxy" in deoxyribonucleic acid) from the corresponding RNA sugar, prior to assembly of the chain. This enzyme probably evolved after the appearance of RNA components on early Earth.

RNA chains are composed of repeating units called nucleotides. Each nucleotide consists of a phosphate and a ribose sugar, to which one of the four "bases" (uracil, adenine, cytosine, and guanine) is appended. While phosphate minerals were common on Earth early in its history, each of the other components has been the target of laboratory simulations to determine how they might have been formed.

The bases appear to have been relatively easy to create. Hydrogen cyanide, a possible ingredient in the early oceans and lakes, reacts in the presence of ultraviolet light to give off adenine. Other cyanide derivatives (along with urea) can produce the other bases. A reasonable natural setting for this chemistry would have been a shallow lake or lagoon, as envisioned by Stanley Miller in his preparation of cytosine.

More challenging to those studying the origins of life has been determining how ribose may have been formed and to explore how it may have reacted with the bases (especially cytosine and uracil) and acquired the phosphate to form RNA. Formaldehyde (the same chemical used to preserve specimens) is a likely prebiotic molecule that reacts with itself to give a very complex mixture of products that includes traces of ribose. A more effective route, however, starts with formaldehyde and a derivative known as gly-colaldehyde phosphate: these react under alkaline conditions to give mainly a ribose compound with two phosphates attached, and the reaction is promoted by certain minerals.

Heating a mixture of ribose with either adenine or guanine to dryness results in some bond formation between the base and the sugar, but this strategy has failed when cytosine or uracil was used in place of adenine and gua-nine. More research is still needed to establish plausible routes to these RNA precursors on early Earth, and some skeptics have even proposed that a simpler type of backbone may have preceded that found in nucleic acids today.

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