The Advent of RNA
EVEN IF WE accept the premises of a thioester world, we are no nearer to identifying the chemical pathways that led from the first building blocks of life to RNA. A possible experimental approach to the problem does suggest itself. Reproduce in the laboratory the primeval mixture of multimers and look for key catalytic activities in the mixture. According to my model, this is the heart of the problem. Protometabolism must have been channeled by the early catalysts the way metabolism is by enzymes today.
Several techniques now exist for making random peptides. One could even go back to the old Wieland procedure, which has the merit of actually using thioesters. Such experiments might not provide the selective conditions that led to the particular subset of multimers assumed by the model, but they would be a step in the right direction. The congruence rule, on the other hand, would help in choosing the kind of catalytic activities for which to search. I am, unfortunately, too far along my own trail to start such an approach. But other laboratories are becoming interested in it.
Meanwhile, we are left to conjecture, using present-day metabolism as a guide. A possible clue is provided by ATP.
ATP plays a key role in energy metabolism. It is also one of the four precursor molecules used in the synthesis of RNA. Here lies the connection. RNA molecules are constructed from nucleotides, which are combinations of phosphate, ribose, and one of four bases: adenine, guanine, cytosine, and uracil. AMP, the parent molecule of ATP, is one such nucleotide. The similarly constructed GMP, CMP, and UMP are the other three. Just as AMP can be phosphorylated to ADP and ATP, the other nucleotides can likewise be converted to GDP and GTP, CDP and CTP, and UDP and UTP, respectively. The pyrophosphate bonds in GTP, CTP, and UTP have the