The “prebiotic” RNA world

I. The “prebiotic” RNA world

The RNA world at large is based on the premise that RNA is the pristine macro- molecular species, from which eventually DNA and proteins are derived (Gilbert,

1986 ; Joyce, 1989 ; Orgel, 2003 ; Woese, 1979 ). This is outlined in Scheme 2.1 . However, the notion of the RNA-world has acquired a twofold meaning in the literature. On the one hand there is a rich and concrete literature dealing with ribozymes, in vitro evolution of RNA, and with self-replicating RNA families – studies and data, that comprise a very important part of modern biochemistry and molecular biology. On the other hand, there is the imaginary side to the RNA world, based on the assumption that a self-replicating RNA family originated spon-

taneously from prebiotic chemistry – see Scheme 2.2 – and started the whole business. Such an assumption forms the basis of what can be called the “prebiotic” RNA world – a kind of intellectual by-product of the RNA world at large.

Despite an early warning by Joyce and Orgel ( 1986 ) about the molecular biolo- gist’s dream (a self-replicating RNA arising spontaneously from the prebiotic soup), this “dream” is generally found in most of the literature dealing with the origin of life on the fringes of the RNA world. It is true that there are some indications in the literature of the possible onset in vitro of ribozymes from partially random RNA libraries. Among the many examples, Joyce and co-workers (Jaeger et al., 1999 ), Szostak and co-workers (Chapman and Szostak, 1995 ), Teramoto et al., 2000 ), as well as Landweber and Pokrovskaya ( 1999 ) using a constant region and

a randomised region (from 29 to 75% in the four cases), were able to detect the formation of de novo RNA with ligase activity. However, in these works RNA is not produced under plausible prebiotic conditions, rather it is obtained transcrib- ing RNA-codifying DNA by means of sophisticated molecular enzymes such as DNA-dependent RNA polymerase. In addition, RNA molecules are not completely random due to the presence of constant regions required for the manipulation of the sample (i.e. cloning, RT-PCR and sequencining). Those are beautiful pieces of

28 Approaches to the definition of life

Prebiotic soup

Spontaneous synthesis

Stereoregular mononucleotides

Non-enzymatic stereospecific polymerization

RNA

Selection

Self-replicating RNA family

Evolution

Ribozymes

Evolution

Proteic enzymes

Catalysis

DNA

Scheme 2.2 Origin of life, in the popularized version of the “prebiotic” RNA world.

work within the RNA-world and in synthetic biology at large, but the relevance of all this for the prebiotic world is by no means granted.

This view is unfortunately also very popular in college textbooks and is often acritically accepted by most undergraduate and graduate students in the life sciences – and by inference by lay people. I say “unfortunately” because the accep- tance of the spontaneous appearance of such a structurally complex and functionally sophisticated RNA molecular family is tantamount to the acceptance of a miracle – one may as well accept more traditional kinds of miracles. One should recognize

that in order for real chemistry to occur many copies (c. 10 10 –10 15 ) of identical RNA molecules are needed, while one can easily calculate that the probability of quite a few identical copies of a specific macromolecular sequence capable of self- replication arising spontaneously from the mixture of monomers is essentially zero. Aside from mathematical considerations, the chemical evidence is that there is until now no ascertained prebiotic synthesis for mononucleotides. Notably, this is still the case, despite the tremendous effort of many brilliant chemists over more than

30 years of investigations. Even if the prebiotic formation of monomers were known, we would not know how to perform an enzyme-free long-chain polymerization, and even less how to make an enzyme-free 3 ′ –5 ′ stereospecific polymerization. Then there is the problem of making many identical copies of the same sequence. In

Chapter 7 , which looks at self-replication, additional reasons are discussed as to why the idea of the spontaneous birth of a self-reproducing RNA is at the present stage not tenable.

29 There is of course still the possibility that some brilliant chemist will soon

II. The compartmentalist approach

discover a prebiotic scenario for making RNA sequences – in a way we all hope that this will be the case, it would indeed be a good day for those studying the origin of life. However, for the time being, the “prebiotic” RNA world is grounded on the above-mentioned dream, and not on solid science.

Why then is there this popularity of the prebiotic RNA world? There are three reasons that come to mind. One is the already mentioned great success of the RNA world at large, which, by inference, gives confidence in the power of RNA. Another reason is that from self-replicating and mutating ribozymes, one can conceive in paper a route to DNA and proteins – and then one has the whole story. A third reason is the lack of a good competitive model – namely the fact that there is no alternative mechanism that is supported experimentally.

All this is no reason to write college textbooks in which a random polymerization of nucleotides magically produces self-replicating ribozymes. There are more and more critics nowadays of this “prebiotic” RNA world, but there is a general consen- sus that RNA was a key molecule for determining – if not the origin of life – early evolution. We will come back to this point later on in this book. I would like now to conclude this section on RNA with something positive, namely two important lessons. One is about the importance of self-replication as a basic mechanism for the beginning of the mechanisms of life. The second, more sophisticated, point, is the recognition that the search for macromolecules that contain both genetic information and catalytic power would greatly simplify any scenario concerning the origin of life.