Insight into RNA origins

UK researchers have offered new insight into the origins of RNA - and possibly life itself - by synthesising activated ribonucleotides from small molecule precursors under conditions that the team says are similar to possible geochemical scenarios on early Earth.

The ’RNA world’ hypothesis is a widely-held view of how DNA-based life may have originated in which RNA - a polymer of activated ribonucleotides - is thought to have preceded DNA. The theory holds that RNA acted as an information-carrying molecule that was capable of catalysing its self-replication to support early life. However, one of the biggest problems of the RNA world hypothesis has been how the nucleotides came to exist in the first place. 

Now, organic chemist John Sutherland and his team at the University of Manchester have offered one of the most plausible solutions to date. Previously, scientists looked at the problem in terms of how the three components of nucleotides - a base, a sugar group, and an inorganic phosphate - could be stuck together. 

’There’s been this subjective assessment which says because they look like that, they ought to be made from those three components,’ says Sutherland. ’What we’ve discovered is that you can synthesise nucleotides from small molecule precursors that are actually sugar-nucleobase hybrids.’

Using their approach, the team demonstrated how nucleotide chains can be built by adding a bit more sugar and then a bit more nucleobase, continuously synthesising chimeric intermediates as opposed to free sugars and nucleobases. What’s more, the researchers achieved high yields of up to 92 per cent. ’This is chemistry that works - it’s robust, predisposed chemistry which is extremely plausible for those of us who actually have it that organic chemistry was central to the origin of life,’ adds Sutherland.

Contested origins 

However, Robert Shapiro, professor emeritus of chemistry at New York University disagrees. ’Although as an exercise in chemistry this represents some very elegant work, this has nothing to do with the origin of life on Earth whatsoever,’ he says. According to Shapiro, it is hard to imagine RNA forming in a prebiotic world along the lines of Sutherland’s synthesis. 

’The chances that blind, undirected, inanimate chemistry would go out of its way in multiple steps and use of reagents in just the right sequence to form RNA is highly unlikely,’ argues Shapiro. Instead, he advocates the metabolism-first argument: that early self-sustaining autocatalytic chemosynthetic systems associated with amino acids predated RNA.

But Sutherland acknowledges the implications of his research in this debate. ’The RNA world is a very restrictive, hypothetical arrangement and one shouldn’t necessarily interpret our results as just supporting an RNA world,’ explains Sutherland.   ’Our work doesn’t preclude metabolism being important, but it suggests that nucleic acids would be central to any early origin of life idea.’

’Of course, it is referring to an event of the past and therefore conclusions will never achieve a level of certainty as in other scientific fields,’ says renowned synthetic organic chemist Albert Eschenmoser. ’But Sutherland’s work is a fundamental study referring to the problem of the origin of life. It is an exemplary piece of how to do synthetic organic chemistry research under very serious constraints of prebiotic chemistry,’ Eschenmoser adds.

James Urquhart