The RNA world

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This chicken-and-egg debate was transformed during the 1980s by a novel discovery: Cech and Altman found that RNA can function as an enzyme - no proteins were necessary. Some RNAs catalyse their own cleavage and their own polymerisation. Orgel had demonstrated some years previously that polynucleotides, particularly RNAs, can catalyse the formation of copies of themselves. These strands of evidence suggested to some scientists that the question "proteins first or nucleic acids first?" was answered: the nucleic acid, specifically RNA, came first. Gilbert and others proposed that for a period on the primitive Earth, RNA molecules manipulated themselves and each other, replicating autonomously. They called this period the "RNA world".

The RNA world hypothesis is now textbook material. There is a consensus that the "RNA world" gave way to "true" life when the RNA started to translate itself into proteins and DNA succeeded it as the repository of genetic information34. But the hypothesis is inadequate. First, it is hard to make key RNA reactions go without external catalysts, and bringing the four bases together for initial synthesis would have been problematic. Second, RNA molecules are fragile and tend to break up unless

34 DNA is chemically much more stable than RNA and is far less inclined to catalyse reactions that will alter it. It is more suitable for making very big polymers that are more or less guaranteed to last. Natural selection would certainly have favoured the replacement of RNA by DNA as genetic material, but it is still far from clear how DNA ever got into the act in the first place.

carefully cosseted. The longer the RNA, the more fragile it is; but a short RNA is relatively useless both as a repository of information and as an enzyme. Perhaps several short RNA molecules working together could have formed a replicating system, but assembly of a number of short RNAs in the same confined space would have been improbable. Third, RNA seems unable to catalyse many of the reactions crucial for energy metabolism. Fourth, as in the case of amino acid selection for protein manufacture, it is not clear how nucleotides with the correct "handedness" were selected for polymerisation. Fifth, there are major differences in the RNA replication mechanisms of archaea, bacteria and eukaryotes, suggesting that these mechanisms had no common ancestry. This throws doubt on the idea that all major branches of life arose from an "RNA world". Finally, it is not clear how the proto-organisms of the "RNA world" were supposed to manage without membranes. There is no indication of internal state, or responsiveness to environment: autonomously replicating RNA, if it ever existed outside a modern laboratory, was not an organism.

Of course, prebiotic "RNA" might have contained ingredients that modern RNA lacks. Some chemical modifications confer remarkable chemical properties on the molecule (as they do on DNA). When bases are modified or novel ones are inserted, or a chain of amino acids is attached to the end of the polymer, RNA can perform or catalyse all kinds of reactions, perhaps including some that simulate energy metabolism. An RNA-protein hybrid might have forged a link between the replication and translation processes we know today. Present-day living cells cannot be persuaded to accept these modified nucleic acids, but that does not mean they played no part in the origin of life. On the other hand, there is no evidence that they did. Modified nucleic acids are interesting to chemists and might be valuable commercially, for instance in manufacturing certain drugs, but whether they make the "RNA world" more plausible is dubious.

Other self-replicating chemical systems have been studied. One of the most interesting discoveries in this field is due to Julius Rebek. He found that when a self-replicating polymer is mixed with inefficiently replicating polymers, together with their building blocks, the best replicators quickly predominate at the expense of their competitors. This result seems obvious with hindsight; a kind of chemical Darwinism. But it might help us to understand how self-replicating chemical systems came to be "selected for" on the primitive Earth. Could an RNA-protein hybrid have developed by such a mechanism? This is speculative, but it is not impossible.

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