The problems associated with the RNA world hypothesis are well known. In the following I discuss some of these difficulties, some of the alternative hypotheses that have been proposed, and some of the problems with these alternative models. From a biosynthetic – as well as, arguably, evolutionary – perspective, DNA is a modified RNA, and so the chicken-and-egg dilemma of “which came first?” boils down to a choice between RNA and protein. This is not just a question of cause and effect, but also one of statistical likelihood, as the chance of two such different types of macromolecule arising simultaneously would appear unlikely. The RNA world hypothesis is an example of a ‘top down’ (or should it be ‘present back’?) approach to early evolution: how can we simplify modern biological systems to give a plausible evolutionary pathway that preserves continuity of function? The discovery that RNA possesses catalytic ability provides a potential solution: a single macromolecule could have originally carried out both replication and catalysis. RNA – which constitutes the genome of RNA viruses, and catalyzes peptide synthesis on the ribosome – could have been both the chicken and the egg! However, the following objections have been raised to the RNA world hypothesis: (i) RNA is too complex a molecule to have arisen prebiotically; (ii) RNA is inherently unstable; (iii) catalysis is a relatively rare property of long RNA sequences only; and (iv) the catalytic repertoire of RNA is too limited. I will offer some possible responses to these objections in the light of work by our and other labs. Finally, I will critically discuss an alternative theory to the RNA world hypothesis known as ‘proteins first’, which holds that proteins either preceded RNA in evolution, or – at the very least – that proteins and RNA coevolved. I will argue that, while theoretically possible, such a hypothesis is probably unprovable, and that the RNA world hypothesis, although far from perfect or complete, is the best we currently have to help understand the backstory to contemporary biology.
This article was reviewed by Eugene Koonin, Anthony Poole and Michael Yarus (nominated by Laura Landweber).
Keywords: RNA world hypothesis, Proteins first, Acidic pH, tRNA introns, Small ribozymes