The description of the appearance of life on the Earth as ‘a near miracle’ does not square, however, with the relatively short length of time that it took to appear (at most 600m years). There are therefore two ways around this problem. Either more plausible abiotic synthesis paths need to be discovered for the creation of the nucleotides, such as those being developed by Geoffrey Zubay at Columbia University, New York, US, or other possibilities for the development of life need to be considered. One proposal that is now gaining ground is that RNA was not the first replicating molecule; that there was a pre-RNA world from which the RNA world developed.
Suggestions for what form this pre-RNA world may have taken are many and varied. But the general idea behind almost all of them is that the first replicating molecule was not RNA, at least not as we would recognise it today, but that whatever form this replicator took it eventually spawned self-replicating RNA, which then went on to usurp its role as the prime replicator on the early Earth. This hypothesis thus neatly bypasses the problem inherent in the prebiotic synthesis of RNA, because the first RNA would have been produced by the original replicators.
Some of the proposed inhabitants of the pre-RNA world are merely simplified versions of RNA, which researchers envisage might have been easier to produce abiotically. For instance, it may be that a form of RNA that could self-replicate without needing all four nucleotide bases would have arisen initially.
Evidence that this idea might at least be feasible came at the end of last year, when Joyce, together with another Scripps researcher, Jeff Rogers, used RNA in vitro selection methods to develop a ribozyme that joined together strands of RNA even though it lacked the cytosine nucleotide, cytidine (Nature, 1999, 402, 323). Joyce and Rogers chose to do away with cytidine for two reasons: it is the least stable of the four RNA nucleotides because of its tendency to undergo spontaneous deamination to uridine; and the uracil nucleotide, uridine, is able to bond with both adenosine and guanosine, which should be sufficient to form the complex RNA structures required for catalytic ability.
In the same vein, researchers have suggested forms of RNA where the ribose sugar backbone of RNA is replaced by another sugar, or in which the furanose form of ribose is replaced by the pyranose form. Indeed, RNA strands that possess a pyranosyl analogue of ribose, known as p-RNA, seem to be better replicators than normal RNA: p-RNA is more stable and less likely to form multiple strand structures that inhibit replication. However, if one accepts that this molecule inhabited the pre-RNA world, it then becomes difficult to see how RNA would ever have gained the upper hand.
Another example is peptide nucleic acid (PNA), where the ribose-phosphate backbone is replaced by amide bonds. PNA can form a stable double helix with complementary RNA, and information can be passed from RNA to PNA and vice versa, showing that the two could have co-existed until RNA gained the upper hand.