Saturday, 17 November 2012

54. The RNA-World Model for the Origin of Life

Modern living organisms depend on both DNA and proteins. But what came first, DNA or proteins? DNA has the codes for the synthesis of proteins, but it itself needs proteins (enzymes) for its creation. A way out of this chicken-or-egg dilemma has been found by the currently popular RNA-world model for the origin of life. According to it, since RNA (a close cousin of DNA in terms of structure etc.) has been observed to act both as an information-storage (replicating) molecule and as an enzyme, life probably started as 'nude replicating RNA molecules'.

This model of the origin of life became popular after of the discovery, made in the mid-1980s by Thomas Cech and coworkers, that certain RNA sequences called ribozymes can act as enzymes, i.e. catalyze reactions. This dual functionality of RNA might have allowed for the existence of an 'RNA species' that could replicate itself and thus seed the beginning of biomolecular evolution.

RNA is indeed known to be involved in a number of fundamental cell-biology processes. All biological cells contain ribosomes, which comprise of as much as ~60% ribosomal RNA (rRNA); the rest ~40% is protein.

Moreover, the ribosome machinery is almost identical throughout the living world; perhaps it existed almost from the beginning of life on Earth. This is an important clue because all life is believed to have had a common ancestor.

According to one version of the RNA-world hypothesis, a different type of nucleic acid, namely pre-RNA, was the first to emerge as a self-reproducing molecule, and was replaced by RNA only later. But it is also true that activated pyrimidine ribonucleotides (two of the four nucleotides constituting RNA are pyrimidines) have been synthesized in the laboratory under reasonable prebiotic conditions.

However, several scientists have expressed reservations about the RNA-world model, as discussed, for example, in a recent Wikipedia article. I shall quote the objections of Stuart Kauffman, author of the 1995 book At Home in the Universe, and the 2000 book Investigations:
  • It is difficult to get RNA strands to reproduce in a test tube. ‘No one has succeeded in achieving experimental conditions in which a single-stranded DNA or RNA could line up free nucleotides, one by one, as complements to a single strand, catalyze the ligation of the free nucleotides into a second strand, melt the two strands apart, then enter another replication cycle. It just has not worked’.
  • Even if life did tend to originate and evolve by the RNA route, naked RNA molecules must have suffered an ‘error catastrophe’ during the replication processes, thus corrupting the genetic message from generation to generation. In present-day cells, such errors (mutations) are kept to a minimum by the so-called ‘proofreading’ and ‘editing’ enzymes. (Such considerations form part of a new subject called 'systems biology'.)
  • RNA-based life, even if it did emerge, was not complex enough to sustain itself. In other words, it was too far from the edge of chaos where complexity thrives best. Why viruses do not have independent life? Why is it that the simplest free-living cells are the so-called pleuromona, and nothing less complex than them? Pleuromona are the simplest known bacteria, and they are complete with cell membrane, genes, RNA, protein-synthesizing machinery, proteins. All free-living cells have at least the minimal molecular diversity of pleuromona. Why nothing simpler exists that is alive on its own? The nude RNA or the nude ribozyme polymerase idea for the origin of life offers no decent explanation for the observed minimum necessary complexity of any life form.

I shall discuss an alternative model of the origin of life in the next post. It is based on the 'metabolism-first' idea (as opposed to the replication-first idea inherent in the RNA-world model). There are many variations of the metabolism-first idea; i.e. metabolism without genes. For example there is the lipids-first model (Segre & Lancet 2000), as sketched in Column B in the figure below. Column A depicts the RNA-first idea.

Phospholipids are known to form lipid bilayers in water, the same structure as in cell membranes. And this is what I wrote in Part 45 about vesicles:

When a giant vesicle, which happens to have a smaller vesicle inside it, is exposed to octyl glucoside, the smaller vesicle can pass through the outer membrane into the external medium (‘birthing’). The resulting injury to the membrane of the host vesicle heals immediately. Addition of cholic acid, on the other hand, induces a feeding frenzy in which a vesicle grows rapidly as it consumes its smaller neighbours. After the food is gone, the giant vesicle then self-destructs (a case of ‘birth, growth, and death’). Such lifelike morphological changes were obtained by using commercially available chemicals; thus these processes should be assigned to organic chemistry, and not to biology or even biochemistry.

The main idea of the lipids-first model invoking vesicles is that initially information was stored in the molecular composition of lipid bodies, and the evolution of more efficient information-storage molecules like RNA and DNA occurred in a later epoch.


  1. I think you should read this paper: Saurav Mallik, Sudip Kundu (2012). The Lipid-RNA World: A Membrane Bound Origin of Ribosome: arXiv:1211.0413 [q-bio.BM]. RNA World hypothesis, though seems to be the only possibility in prebiotic world, but it can not stand on its own. It requires modifications. I hope this paper suggests what that modification should be...