#8 Ribozymes?

Let us look in detail at the catalytic properties of RNA.  The single intron of the large ribosomal RNA of Tetrahymena thermophila (a ciliated protozoan) has self-splicing activity in vitro.  This RNA was named a ribozyme because it is an RNA that acts like an enzyme.   However, most, if not all other RNA-based catalytic reactions are thought to take place in conjunction with proteins.  Spliceosome and ribosomal RNAs have the ability to catalyse peptide bond formation, but they are better described as catalytic ribonucleoproteins than ribozymes since they do not make the role of proteins unnecessary.

Large ribozymes mostly include members of the group I and group II intron family found in algae, fungi and plants.  These are self-splicing introns.  Group I ribozymes use an external guanosine (G) nucleotide as a cofactor and group II ribozymes require an active site containing Mg2+ ions for catalysis.  Group I and group II introns self-splice under certain conditions in vitro, but require proteins to fold the intron RNA into the catalytically active structure in vivo.  The proteins are either encoded by the introns themselves or encoded by other genes (Allison 2007, pages 69-73 and 455-457).

Small ribozymes found in viruses and viroids act as riboswitches involved in gene regulation.  The other small ribozymes are involved in self-replication of the circular RNA of viruses (Allison 2007, page 75).

From this detailed account it can be seen that ribozymes represent a limited case found in a few organisms.  Intron-splicing by a ribozyme is catalytic and leads to modification of the RNA itself.  This characteristic contradicts the classic definition of an enzyme as being a substance that increases the rate of a chemical reaction, but is not itself changed in the process.  Therefore, a ribozyme does not simply act as an enzyme made of RNA rather than protein.

The autocatalytic nature of RNAs cited as ribozymes is highly questionable when one pays attention to detail.  It emerges that in vivo none of these RNAs act alone – their catalytic properties are dependent on proteins to initiate folding that makes the RNA structure catalytically active.  Therefore, RNA ribozymes do not act alone, but in conjunction with proteins.  It looks like proteins won’t go away.

I have not used the word hypothesis in connection with RNA World because it is untestable.  It is a speculation upheld by an almost mystical view of Natural Selection in which Natural Selection acts in a world of personified molecules that ‘want’ to replicate.  Shapiro accuses the adherents of these origin of life theories as creating a mythology whose truth cannot be challenged even in the face of adverse evidence (Shapiro, 1986, page 32).

“In the origin-of-life field, a particular theory or point of view is frequently elevated to the status of a myth.  It is then treated only as a doctrine to be validated, and not one to be challenged.”  (Shapiro 1986, page 33).

#7 RNA World

Watson and Crick published on the double helix structure of DNA in 1953.  By then it was known that the cell was not just a collection of molecules in cytoplasm bounded by a membrane, but a miniature world of metabolic pathways precisely regulated by an information-carrier: the DNA molecule.

Over the next decades, DNA replication was found to be facilitated by complementary base-pairing; the transcription of gene sequences was found to involve RNA and protein transcription factors; and the role of genes in regulatory feedback networks was investigated.  The composition of transfer RNA was determined by R. W. Holley in 1965.

It became apparent that the probability that the genetic system evolved by chance, even given the age of the Earth counted in thousands of millions of years, or even given the expanse and duration of the entire universe, is virtually nil.

Calculations showed that if mutation is truly random and unguided, any way of trying to derive a functional genetic system from it, ends in massive error catastrophe (Eigen and Schuster).  Probability became a favourite subject of Creationists and NeoDarwinists tried every possible way of getting round it.

There was also the chicken and egg problem under a new guise; DNA is transcribed, edited and translated by RNA, protein transcription factors and enzymes that are themselves DNA products.  Which came first, DNA or RNA and proteins?  In the genetic system of all known free-living organisms, no one component could have arisen without the other components.  Calculation of the probability that all the different components of the system arose by chance at once shows that this would be nothing short of a miracle.  Monod writes that the origin of the genetic code is a veritable enigma: 

“The code is meaningless unless translated.  The modern cell’s translating machinery consists of at least fifty macro-molecular components which are themselves coded in DNA: the code cannot be translated except by products of translation.  It is the modern expression of omne vivum ex ovo.  When and how did this circle become closed?”  (Monod 1970, page 135).

Thus, it was proposed that there once lived a form of life that was simpler than anything known.  The hypothetical first cell, the ‘progenote’, had a genome composed only of RNA.  RNA carried the genetic information and catalysed its own replication.  This proposition is called RNA World. 

The idea that there could have existed a form of life run by RNA was first voiced by Carl Woese in a book entitled The Genetic Code in 1967[1], and further elaborated in 1977.  The idea was again expressed in an article by Francis Crick in 1968[2].  However, the idea of RNA World was really put together by Walter Gilbert in 1986[3] after the discovery of ribozymes.  The hypothesis has had mixed fortunes, but it has now become very popular with its supporters speculating that at a hypothetical stage in the evolution of life some 4000 million years ago, life would have been represented by autocatalytic, self-replicating RNA molecules.

The central dogma of molecular biology – ‘DNA makes RNA makes protein’ – is therefore reversed by origin of life theorists, with DNA appearing last.

Investigations to support RNA World have included experiments to get single-stranded RNA to copy itself in a test-tube.  These attempts have ended in tangles of RNA and persistent failure.  Replication and single-strandedness appear to be incompatible.  The idea that RNA might have had a catalytic function in the place of protein enzymes has been encouraged, however, by the discovery that some RNAs catalyse chemical reactions in the cell.

[1] Carl Richard Woese (1967) The Genetic Code: The Molecular Basis for Genetic Expression  Harper & Row

[2] Francis Crick (1968) The Origin of the Genetic Code.  Journal of Molecular Biology Vol. 38 (3), pages 367-379.

[3] Gilbert, W. (1986)  The RNA World.  Nature Vol. 319, page 618.