The molecular maps that exist today, the ones that continually improve and become more accurate, already seems inextricably complex (See Also: New Tissue Atlas Shows Protein Distribution Within the Human Body). We have the concepts of DNA transcription down, and the events of translation are well understood. What can be difficult to imagine is how protein synthesis came to be in the first place when so many interlocking pieces are involved and required. Obviously these systems could not have worked without the apparatus already in place, so how did it all come about?


LIKE MOLECULAR TOY-MAKERS, ribozyme researchers create tools with evolutionary, diagnostic, and therapeutic applications. (Source:, Illustration by: Ned Shaw) 

Experiments performed In vitro have produced rudimentary RNA molecules from scratch. These experiments revealed the nucleotide sequences for those RNAs, had a high affinity for a particular amino acid that are able to sufficiently bind to amino acids and catalyze a reaction [1,2]. For a protein to be even classified as a catalyst, it first needs a surface with unique curves that allow it to serve and be recognized as an enzyme. These experiments showed that a molecule of RNA could be molded into a functional shape. As we talked about previously with Porphyrin, some proteins are able to position metal ions at their active sites, which provide them with unique cellular properties.

Similar functional studies have been performed, each one producing its own rare type of RNA molecule that can each catalyze a surprisingly wide variety of biochemicals (see Table 1). These so called ribozymes are similar to proteins in that they can undergo conformational changes in response to a molecule, which can activate their catalytic activity.

Once a ribozyme has been created, they reportedly have their own complimentary isoform that also has a unique set of properties. Probably the most familiar of all ribozymes is the ribosome, a heterodimer of 1+ ribozymes and smaller support proteins. Ribosomes are tasked with translating messenger RNA (mRNA) into proteins.

While we debate on and on about the structure and function of all the molecules and how they came to exist today, it's not at all implausible to suggest that a world containing a high level of biochemical sophistication could happen at all without the help of some early pre-formed molecules of RNA that could polymerize the basic amino acids, guanine, cysteine, arginine and tyrosine. Conceivably then, in that primordial, far off world, any self-replicating RNA molecule could help guide the construction of a more complete, useful polypeptide and would have had selective advantage in the evolutionary struggle for survival.

Table 1. Some Biochemical Reactions That Can Be Catalyzed by Ribozymes [3]

Peptide Bond formation in protein synthesis Ribosomal RNA
RNA cleavage/ligation Self-splicing RNAs
DNA cleavage Self-splicing RNAs
RNA splicing Self-splicing RNAs, perhaps RNAs of the spliceosome
RNA polymerization In vitro selected RNA
RNA and DNA phosphorylation In vitro selected RNA
RNA alkylation In vitro selected RNA

The enzymatic properties of RNA and the fact that they still exist, lends credibility to the idea that RNA cleared the path to the formation of cells. James Watson famously praised Sir Fancis Crick for originally suggesting this as a possibility [4]:

"The time had come to ask how the DNA RNA protein flow of information had ever got started. Here, Francis was again far ahead of his time. In 1968 he argued that RNA must have been the first genetic molecule, further suggesting that RNA, besides acting as a template, might also act as an enzyme and, in so doing, catalyze its own self-replication."


Francis Crick

Crick (pictured above) was well ahead of his time in his reasoning, because the enzyme properties of RNA were not discovered until 1986 by Nobel-prize winning scientist Thomas R. Cech [5].

Today, in the present day, RNA has naturally adapted to match amino acids to their particular codon, and have been catalyzing histones for DNA modification (and other site-specific amphipathic reactions) for many millions of years.

Amphipathic being the physical property of a molecule consisting of one part hydrophobic and another part hydrophilic a rather bi-polar molecule by its very nature but the flexibility of RNA when compared to other molecules is exactly what provides it with a unique portfolio of abilities not available to other molecules.

This interpretation may be controversial, but in the earliest cells, these pre-RNA molecules would have combined and recombined according to their existing structure or catalytic function. These pre-RNAs, conceivably, would have been replaced by cell-based RNA systems, and eventually by the much harder to build DNA as the main repository of genetic information. Proteins now perform the vast majority of catalytic functions in cells. While RNA is the go-between molecule, and although it still retains its catalytic properties, especially for a handful of crucial reactions, the deoxyribose sugar of DNA is still natures best way of protecting genetic information.



[1] Orgel L., Origin of Life. A simpler genetic code: amino acids as cofactors in an RNA world. Science. (2000) 290, pp. 1306-1307.

[2] Szathmary E., The origin of the genetic code: amino acids as cofactors in an RNA world. Trends In Genetics. (1999) 15, pp. 223-229.

[3] Table adapted from E.A Schultes and D.P Bartel, One sequence, two ribozymes: implications for the emergence of new ribozyme folds. Science. (2000), 289, pp. 448452.

[4] James D. Watson, "Prologue: Early Speculations and Facts about RNA Templates," p xv-xxiii, The RNA World, R.F. Gesteland and J.F. Atkins, eds. Cold Spring Harbor Laboratory Press, 1993. p xxiii.

[5] Thomas R. Cech, "A model for the RNA-catalyzed replication of RNA" [abstract], p 4360-4363 v 83, Proc. Nat. Acad. Sci., USA, 1986.