Were the building blocks of life hiding in plain sight?

Surprisingly simple experiments conducted under everyday conditions may have finally solved the mystery of how components of DNA and RNA formed from chemicals present on the Earth in the days before life existed, claims research published today in Nature Communications.

As part of their study, a team of scientists from the NSF/NASA Center for Chemical Evolution at the Georgia Institute of Technology conducted a series of basic laboratory reactions in water, and were able to synthesize what they believe may be good candidates for the missing links of life.

When the components they created joined together, the end products even resembled RNA, they explained in a statement. With additional research, the study authors believe they could discover most of the chemistry that caused life to emerge from the primordial soup, and perhaps even gain new insight into the possibility that living organisms exist on other worlds.

Two simple, abundant compounds may hold the key to RNA formation

The research, which was funded by NASA and the National Science Foundation, centered on the search for RNA’s origins and involved two potential chemical forerunners of its nucleobases, the nitrogen-containing biological compounds believed to be the basic building blocks of this nucleic acid: a pair of molecules known as barbituric acid and melamine.

Using these molecules, Nicholas Hud, director of the Center for Chemical Evolution as well as a professor in the Georgia Tech School of Chemistry and Biochemistry, and his colleagues formed proto-nucleotides that bore a strong resemblance to nucleotides found in RNA, which appears to indicate that they may have been the predecessors of those nucleotides. Melamine and barbituric acid would both have been abundant on the prebiotic Earth, according to Hud.

Due to the properties of these molecules, and their resemblance to RNA nucleotides, a handful of scientists have speculated that they did likely play a role in the formation of the nucleic acids, but Hud’s team believes that it is too early to reach such conclusions. First, they would need to show a mechanism through which their lab-created nucleotides could turn into the existing nucleotides found in RNA, explained study co-author Ram Krishnamurthy.

That, Krishnamurthy said, would be “a complex path that we’d have to at least design on paper, and we’re not there.” Even so, he said that he and his colleagues are excited about their findings. “There are umpteen possibilities of how that mechanism could have happened. Barbituric acid and melamine may have been place holders that dropped out and allowed adenine and uracil to come together with ribose.”

First ever spontaneous formation of Watson-Crick pairs in water

Discovering how the nucleobases adenine and uracil combined with the sugar ribose to form RNA could help researchers solve one of the great mysteries of chemical evolution, the research team explained, and the formation of nucleotides from possible proto-nucleobases and ribose is one huge step forward in the search for the chemical originals of life.

While scientists had previously combined nucleobases with other sugars, those reactions were far less efficient that the latest batch, according to the study authors. These ones occurred quickly, and created nucleotides that spontaneously paired with one another in water, forming hydrogen bonds similar to the Watson-Crick base pairs found in RNA helixes.

The nucleotides then when on to form long, supramolecular assemblages that resembled strands of RNA when viewed under a high resolution microscope. The experiment marked the first time that a chemical reaction involving water resulted in the spontaneous formation of Watson-Crick pairs. “We’re getting close to molecules that look the way life may have looked in early stages,” said Krishnamurthy.

“It works even better than we thought. It’s almost too easy,” Hud added. However, he noted that there was one small hiccup: “The reaction does not work as well if barbituric acid and melamine are present in the same solution before reacting with ribose,” he explained, “because their strong attraction for each other can cause them to precipitate.” While this means each reaction had to be completed separately, this would not have precluded such reactions from occurring naturally, in separate locations on the prebiotic Earth.

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Image credit: Fitrah Hamid, Georgia Tech

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