by Greg Mayer
A paper in this week’s Nature (abstract only; here’s a NY Times piece on it) reports fascinating and important work on prebiotic synthesis of the building blocks of RNA by Matthew Powner and colleagues at the University of Manchester.
Building on an idea that can be traced back to Darwin’s notion of a “warm little pond“, chemists have sought for the origins of life in the chemistry of simple molecules– water, ammonia, methane, etc.– in an early Earth environment. Much progress has been made. It was found that lipids spontaneously aggregate into cell-like bilayers, that organic compounds are found in meteorites left over from the early history of the solar system, and, in a type of now classic experiment first conducted by Stanley Miller and Harold Urey, that quite a variety of organic compounds, including a number of biologically important ones, could be generated from these simple molecules under hypothesized early Earth conditions. Despite this progress, much remained to be understood. In particular, most life worked with DNA as the information-containing molecule, proteins as the work-horse molecules catalyzing chemical reactions, and RNA as a medium for transferring the information from the DNA to the proteins. But DNA needed proteins for its information to be expressed, and proteins needed the information from DNA to be produced– which came first?
In the 1980s, Thomas Cech and Sidney Altman indpendently discovered what seems to be the answer (or at least part of it): RNA cannot only carry information, it can also catalyze chemical reactions: it can perform the job of both DNA and proteins! Prior to the modern DNA-RNA-protein scheme, there was a living world of RNA alone, the so-called (by Wally Gilbert) “RNA World”. This was a major observational and conceptual step in our understanding. The prebiotic origin of RNA thus became a major problem. That’s where Powner et al. come in.
RNA, like DNA, is composed of many repeating units which come in four varieties (the sequence of the four types is how the information is stored), and in RNA these units are called ribonucleotides. Each of the repeating units is composed of a sugar, a nitrogenous base, and a phosphate group. For many years, attempts to find a synthetic pathway to ribonucleotides from simpler precursors were, at best, incomplete. These attempts tried to assemble the three components, but could not join the sugar with the base. What Powner et al. have done is cut this Gordian knot, and arrived at a synthesis from simpler precursors that proceeds via intermediate molecules which are neither sugars nor bases (2-amino-oxazole, then arabinose amino-oxazoline, to be precise). Under plausible conditions of pH, temperature, etc., a high yield of ribonucleotides can be had.
There are still many steps in the origin of life that need to be understood– polymerizing the ribonucleotides into a proper RNA molecule, for starters– but this is undeniably a key finding. Some hypothesize that even simpler information/catalytic molecules– the “Pre-RNA World”– preceded RNA; only future work will tell. John Sutherland, one of Powner’s coauthors, and in whose lab the work was done, worked on the problem for twelve years before he found the solution. What if he had given up after ten? Could we have concluded that no synthesis was possible? No. This work demonstrates the futility of all the various sorts of arguments– the argument from design, the God of the gaps, the argument from personal incredulity– that rely on ignorance as their chief premise.