Posted by: Dan | November 2, 2006

Viral and RNA Worlds Collide

Unfortunately it’s sometimes difficult to keep up with the pile of papers on my desk, and blogging about them. But I’m getting around to them – and one that I particularly wanted to come back to was originally recommended to me a while back by Ivy Privy: “The Two Ages of the RNA World, and the Transition to the DNA World: a Story of Viruses and Cells”.

Patrick Forterre bases this thesis on the view on the following assumptions: (i) that a world of free molecules likely could not have evolved to such an extent to produce a set of complex ribozymes able to synthesize proteins; and therefore, (ii) a cellularization (or encapsulization of genetic material by membranes) was likely required early on in the pre-biotic world. As Forterre notes, however, as a common view on the origin of life suggests that cellularization only occurred after the divergence of the three domains of life (Archaea, Bacteria, and Eukarya) – a view seemingly supported by dissimilar membrane composition across these domains.

In particular, the previous view suggests that only a late emergence of membranes could explain why archaeal lipids are so different from eukaryotic/bacterial lipids, which have opposite stereochemistry and different backbones for the long carbon chains). Forterre addresses errors with this paradigm, however:

However, this hypothesis, which implies an acellular Last Universal Common Ancestor (LUCA), is contradicted by phylogenomics analyses showing that several membrane-related proteins were already present in LUCA. This is the case for some enzymes involved in lipid biosynthesis, for the signal recognition particle, and for the V/F-ATPases (for recent review, see [Pereto et al., 2004]). In fact, cellularisation most likely arose much earlier. It seems difficult (if not impossible) to imagine the early development of an elaborated metabolism in the absence of cellular confinement. Let’s remind that such early metabolism in the RNA world should have been able to produce at least precursors for RNA and lipid syntheses, as well as the associated energy production required to perform these reactions. Accordingly, I will define here the RNA world as a biosphere of cells with RNA genomes (RNA cells). This RNA world started with the first RNA-cell and was over when all its cellular descendants were eliminated in the Darwinian competition by cells with DNA genomes (DNA-cells)

Having established that as the framework for his hypothesis, Forterre enumerates a small handful of crucial transition steps in the history of the RNA world: the first replicating RNA-cell, the invention of the ribosome, and the first DNA cell – with before and after the invention of the ribosome as the defining event separating the “two ages of the RNA world.” As we know that the RNA moiety of the ribosome is responsible for the formation of peptide bonds in modern cells, the emergence of the ribozyme at the beginning of the first age (the first replicating RNA-cell would have possessed ribozymes) constitutes the ancestral ribosome. So that’s not a problem for Forterre’s thesis.

From this, he asks the following question: “Did DNA appear during the first or second age of the RNA world?”

Again, I agree with Forterre’s conclusion that DNA is essentially RNA modified by proteins (ribonucleotide reductases and thymidylate synthases), which would have arisen in the second age of the RNA world. Furthermore, Forterre makes a strong case that complex cells with sizable RNA genomes could have existed in the second age.

Where Forterre’s thesis gets really interesting, however, is in his explanations of how the invention of DNA might have occurred – his viral hypothesis. He sets this explanation up with the following vision of the RNA world:

My vision of the RNA world is thus one of coevolving populations of very diverse RNA cells, and of RNA viruses with a variety of complex relationships and molecular mechanisms which have disappeared today, except for those which were retained int he first DNA cell or in viruses that later on infected its descendents.

This sets up the viral hypothesis iteslf:

… the substitution of RNA by DNA as cellular genetic material appears to be justified in order to allow genome size to increase in the course of evolution (the larger apparently the better). DNA-cells with enlarging genomes will become more complex and finally out-compete their RNA-based ancestors. However, this kiind of argumentation is not valid from an evolutionary point of view. It’s like to arge that features were invented in Dinosaurs in order to prepare for the future flight of birds! In a Darwinian scheme, one has to identify the seletion pressure that first triggered the evoltuionary process by bringing an immediate benefit to the organism in which the innovative mutation(s) appeared. An obvious selection pressure for an organism to modify its genome can be to protect it from attacks by hostile competitors. Chemical modification of its RNA genome into something “new”, immune to RNAases, could have given an immediate benefit to an organism fighting for its life in the jungle of the second age of the RNA world. The principle of continuity suggests that such organism was an RNA virus, since we know that some modern DNA viruses have modified their genome precisely for this purpose (for intence via methylation, hydroxymethylation or even more complex chemical modification (Warren, 1980). It is thus reasonable to think that viruses were also the promoters of previous genome modifications, from RNA to U-DNA, and from U-DNA to T-DNA.

I have some serious disagreements with precepts in this section. First off, he completely discounts the non-adaptive evolutionary mechanisms that could have been responsible for complexification of RNA-cells, and from there to immediate adaptive benefits of subsituting the more stable DNA for RNA in increasingly complex cells. This stochastic acquisiton of robust genetic fidelity could have occurred in much the same way that Michael Lynch has explained that epigenetic regulation and modularity could have evolved into modern eukaryotic gene structure.

So, while I disagree that viruses are solely responsible for the advent of genome modifications, the diversity of viruses and their genetic structures does strongly point to some role for them in these events. That’s an intuitive conclusion however, admittedly.

Forterre continues to use this viral hypothesis to explain dissimilarities between the three domains of life by the “three viruses-three domains” hypothesis. The problem, as Forterre describes, is that it is unclear “why Archaea and Eukarya share homologous informational proteins, whilst Bacteria and Eukarya share homologous membrane structure and composition,” and offers the following as a reconciliation between these facts, that:

Archaea, Bacteria, and Eukarya originated from different RNA cells lineages which acquired independently their DNA geneomes from three DNA viruses; as a consequence, LUCA was an RNA-cell of the second age, in agreement with earlier suggestion by Woese (1983) who call it a progenote.

As I questioned the absoluteness of his viral hypothesis already, I don’t agree strongly with this “three viruses-three domains” hypothesis much either. But, I think, some role here for viruses and horizontal gene transfers in getting from LUCA to three domains is pretty hard to disagree with, given the evidence available to us.

Right or wrong, however, this is certainly a very intriguing series of hypotheses.

References:

  • The two ages of the RNA world, and the transition to the DNA world: a story of viruses and cells. Forterre P. Biochimie. 2005 Sep-Oct; 87(9-10):793-803. Pubmed
  • Ancestral lipid biosynthesis and early membrane evolution. Pereto J, Lopez-Garcia P, Moreira D. Trends Biochem Sci. 2004 Sep; 29(9):469-77. Pubmed
  • Modified bases in bacteriophage DNAs. Warren RA. Annu Rev Microbiol. 1980; 34:137-58. Pubmed
  • The primary lines of descent and the universal ancestor. Woese CR. Evolution from Molecules to Men, Cambridge University Press, Cambridge, 1983, pp. 209-233. Amazon.

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