Tuesday, November 25, 2008

Was a triple helix the precursor to RNA in the origin of life?

original article:

Peptide nucleic acid (gold) readily enters DNA's major groove to form triple-stranded and other structures with DNA, allowing it to modify the activity of genes in new ways.
Jean-Francois Podevin

Origin of Life?
A major goal of these efforts to create life de novo in the laboratory is to better understand how life may have started on earth. Considering the detailed microbiology of contemporary life-forms, it seems very clear that RNA is probably more primordial and central to life than DNA and proteins. This one molecule can carry both the genotype (the genetic sequence information) of an organism and the phenotype (catalytic functions). For this reason as well as other evidence, many scientists now accept the idea that our DNA/RNA/protein world was preceded by an RNA world [see “The Origin of Life on the Earth,” by Leslie E. Orgel; Scientific American, October 1994].

Yet it is very unclear how primitive prebiotic conditions could have produced RNA molecules, in particular the sugar ribose in the RNA backbone. Further, even if RNA molecules were produced, RNA’s very poor chemical stability hardly would have allowed the molecules to survive unprotected long enough to play a central role in the initial chemical evolution of life. Thus, a molecule like PNA appears very attractive as a candidate for a pre-RNA world: it is extremely stable and chemically simple, and it carries sequence information.

In 2000 Stanley L. Miller, famous for his seminal experiments more than 50 years ago showing that amino acids can form under conditions believed to simulate those on the primitive earth, identified precursors of PNA in similar experiments. Researchers have also shown that sequence information in a PNA oligomer can be transferred by “chemical copying” to another PNA oligomer or to an RNA molecule—processes needed for a PNA world and then a following transitional PNA/RNA world. Admittedly, it is a long leap from these scanty observations to building a strong case for a pre-RNA world based on PNA or some very similar molecule, and for the hypothesis to have any legs at all, scientists must uncover PNA molecules possessing catalytic activity.

Much remains to be learned about PNA 15 years after its discovery: Are catalytic PNA molecules possible? What is a good system for delivering therapeutic PNA into cells? Can a totally alien, PNA-based life-form be created in the lab? I am confident these questions and many others will be well answered over the next 15 years.

In addition to fomenting exciting medical research, these amazing molecules have inspired speculations relating to the origin of life on earth. Some scientists have suggested that PNAs or a very similar molecule may have formed the basis of an early kind of life at a time before proteins, DNA and RNA had evolved. Perhaps rather than creating novel life, artificial-life researchers will be re-creating our earliest ancestors.

Yet a genetic replication system is only one component of life, albeit a central one. The essence of life is a network of chemical reactions functioning in a state that is relatively stable yet not in equilibrium and that is open to both inputs and outputs [see “A Simpler Origin for Life,” by Robert Shapiro; Scientific American, June 2007]. A major challenge will therefore be to incorporate the self-replicating molecule in a larger system that carries out other catalytic activity and has a metabolic cycle and to integrate the system with a physical compartment such as a lipid vesicle, forming what some researchers call a “protocell.

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