Forming a double helix prevents the RNA from going round in circles (Image: Laguna Design/SPL)

The primordial soup that gave birth to life on Earth may have had an extra, previously unrecognised ingredient: a “molecular midwife” that played a crucial role in allowing the first large biomolecules to assemble from their building blocks.

The earliest life forms are thought by many to have been based not on DNA but on the closely related molecule RNA, because long strands of RNA can act as rudimentary enzymes. This would have allowed a primitive metabolism to develop before life forms made proteins for this purpose.

RNA strands are formed from building blocks called nucleotides linked together head to tail in a long chain. This happens easily if the nucleotides can bind to another RNA strand that guides their assembly. However, the earliest RNA molecules to form, billions of years ago, would have had no pre-existing RNA to guide them.


Round in circles

Till now, attempts to mimic this first synthesis have always hit a fatal obstacle: instead of binding to the tail of a new nucleotide, the head of a growing chain latches onto its own tail instead. This tendency to form circles keeps RNA molecules from growing much longer than three to six nucleotides – far too short to function as enzymes.

“That is a big problem,” says Nicholas Hud, a chemist at Georgia Institute of Technology in Atlanta. “How do we get a molecule long enough to do something interesting?”

The answer, Hud thinks, may be the presence of a “molecular midwife” – a molecule that nestles between adjacent nucleotides and encourages two growing RNA strands to bind together in a double helix. Since this double helix is much stiffer than a single RNA strand, it is less likely to bend around on itself and form a circle.

If the concentration of molecules in the solution later decreased – as, for example, if rain diluted a primordial puddle – the midwives would tend to slip back out of their slots in the RNA molecule. This would allow the two RNA strands to separate, leaving exactly the sort of long, single-stranded RNA molecule that might act as a catalyst in the RNA world.

Double helices

Sure enough, when Hud and his colleagues added ethidium – which is known to slip between a double helix – to a solution of nucleotides, they found that they joined up into long double helices instead of short circles.

The team studied DNA nucleotides, because the resulting chains are easier to work with, but the same should apply for RNA, they say.

Ethidium itself is a rather complicated molecule with several benzene-like or “aromatic” rings, and is unlikely to have been available to fill this role in the primordial soup. However, molecules found in ancient meteorites suggest that the prebiotic Earth was rich in compounds with a similar structure. Hud’s next challenge is to show that some of these polycyclic aromatic molecules can indeed help RNA molecules assemble.

“Ethidium demonstrates the principle. Is there something among that mix that serves the same purpose?” says Gerald Joyce, a biochemist who studies the origin of life at Scripps Research Institute in La Jolla, California.

Journal reference: Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0914172107