LONDON - Chemists in Switzerland and the U.S. have made a variant of ribonucleic acid that could, in principle, have been a primordial precursor of RNA. This new type of molecule comes by the name of TNA, which stands for (L)-alpha-threofuranosyl oligonucleotide.
The researchers, working at the Scripps Research Institute in La Jolla, Calif., and in Zurich, Switzerland, have shown that complementary strands of TNA form double helixes using Watson-Crick base pairing. These molecules are also able to pair with RNA and deoxyribonucleic acid (DNA).
Albert Eschenmoser, retired professor of chemistry at the Eidgenossische Technische Hochschule in Zurich, told BioWorld International that the studies of his research group are designed to find out more about why life on Earth uses RNA and DNA as its genetic material, rather than other types of molecules. He said, "Chemists can imagine what alternative types of nucleic acid molecules could have been formed using the same types of chemical reactions and it is these variant molecules which we have evaluated, looking above all for their capability to carry out base pairing."
The results of the research by Eschenmoser and his team are reported in the Nov. 17, 2000, Science in a paper titled "Chemical Etiology of Nucleic Acid Structure: the a-Threofuranosyl (3'(r)2') Oligonucleotide System."
Commenting on the paper in the same issue of Science, Leslie Orgel, of the Salk Institute for Biomedical Study, also in La Jolla, suggested that, in principle, TNA could have been a precursor of RNA. He also wrote that, whether or not TNAs are likely precursors of RNA, the results warrant further attempts to identify even simpler RNA analogues.
Eschenmoser and his group have been systematically synthesizing and then evaluating polymers that are analogues of RNA but which have a backbone formed of sugars other than ribose molecules. For the study reported in Science, they used sugars with only four carbon atoms per molecule - tetroses - rather than those with five carbon atoms per molecule, which are known as pentoses.
"The tetrose-based oligonucleotides," they wrote, "show efficient base pairing which is similar to that of pentose-based RNA with regard to specificity, strand orientation, and pairing strength. In addition, TNA oligonucleotides of the L-series are capable of cross-pairing with RNA and DNA."
They speculated that TNA could "potentially serve as a template in nonenzymic template-directed formation of RNA sequences." In other words, Eschenmoser said, because TNA can cross-pair with RNA and DNA, it is able to communicate with them and exchange sequence information. "This is a very important property," he said. "Furthermore, from a structural point of view, this new system is simpler than RNA or DNA, and the simpler the system, the higher its chances of forming under primordial natural conditions."
No one knows, Eschenmoser added, if the first RNA molecule formed as part of a living world where life was completely different to life on Earth today, or whether it arose in a non-living world. He said, "It can be argued that RNA is probably too complicated to allow its formation from a non-living world. Therefore it is of interest to know that there are simpler molecules that could in principle fulfill the same function as RNA and that could have existed in a non-living world. For this reason, these molecules deserve more detailed study, and we are planning to carry out further experiments on them."
Eschenmoser would not discuss how significant he deemed his finding. "If it is important or significant that we gain a better understanding of how life originated, then even a small contribution toward that understanding can be significant," he said.