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When we analyzed the mixture of meteoritic organics, we found that some of the compounds were short-chain fatty acids, soaplike molecules that feature a tail of 9 to 13 carbon atoms. This meant that we no longer needed material from precious meteorites to carry out experiments; we could investigate the properties of the pure compounds purchased from chemical-supply companies. We began with decanoic acid, a 10-carbon fatty acid, and found that it readily produced vesicles similar to those produced by the meteorite extracts. The next question was whether such compartments could encapsulate larger molecules to produce protocells, which are defined as encapsulated systems of molecules–like RNA–that have the potential to act as catalysts and carriers of genetic information. This turns out to be so easy that it could be done for a high-school science fair. If the microscopic vesicles are mixed with large molecules like proteins or nucleic acids, then put through a dry-wet cycle, about half of the large molecules end up inside the vesicles. The glowing lipid vesicles shown in the right-hand panel of the micrograph are composed of decanoic acid surrounding DNA molecules.

The bottom line is that protocells are very easy to produce by simple self-assembly processes. It follows that such structures would also be expected to occur in a prebiotic setting.

Third Milestone: Polymer Synthesis
All life today uses enzymes to catalyze the synthesis of polymers. And nearly all polymeric molecules of life, including proteins and nucleic acids, are synthesized from monomers that are chemically activated–that is, they gain the energy to undergo polymerization–through complex metabolic processes that extract the equivalent of a water molecule from each one. Ribosomes link activated amino acids through peptide bonds to produce proteins, and enzymes called polymerases catalyze the formation of ester bonds between activated nucleotides to produce nucleic acids.

Nothing nearly this complicated could have happened before life began, but a variety of simpler reactions can also produce interesting polymers. For instance, James Ferris, at Rensselaer Polytechnic Institute in New York, showed that a clay mineral called montmorillonite promotes the synthesis of polymeric RNA from activated nucleotides. The mineral surfaces adsorb and organize the nucleotides, which then zip up into polymers. Furthermore, once RNA molecules are formed, they can undergo a kind of limited replication process that does not require enzymes. Leslie Orgel and his associates at the Salk Institute demonstrated in the 1980s that chemically activated nucleotide monomers line up on synthetic RNA templates by Watson-Crick base pairing, as they do in the double helix of DNA, and then polymerize into a second strand of RNA.

The seminal observations of Orgel, Ferris, and others clearly suggested that something like RNA might have been the first polymer to be associated with life processes. Additional evidence was provided when Thomas Cech at the University of Colorado and Sidney Altman at Yale found that certain types of RNA had catalytic properties, a discovery for which they shared a Nobel Prize. Such RNA molecules, now referred to as ribozymes, can make and break specific chemical bonds within their own structure rather than depending on protein enzymes. The discovery of catalytic RNA led Nobel-winning chemist Walter Gilbert at Harvard to propose an “RNA World,” positing that life did not begin with the complex systems of DNA, RNA, and proteins that characterize all life today. Instead, RNA molecules could have served as catalysts as well as storing and transmitting genetic information. The RNA World concept dominates current thinking about the origin of life. Research groups led by Gerald Joyce at the Scripps Research Institute, David Bartel at the Whitehead Institute, and Peter Unrau at Simon Fraser University are attempting to incorporate RNA into a self-replicating system of molecules. Significantly, they often employ a technique in which evolutionary principles are used to select specific catalytic activities from mixtures containing trillions of different RNA molecules.

That brings us to the next milestone.

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Credits: Chris Buzelli, David Deamer

Tagged: Biomedicine

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