New study identifies possible ancestors of RNA

New study identifies possible ancestors of RNA
Which molecules formed RNA, and can we use them to identify where life may form in the universe? Credit: NASA/Jenny Mottar

Researchers from the Georgia Institute of Technology may have made headway in helping determine the origin of life by identifying three different molecules that self-assemble to form a molecular structure with features characteristic of modern RNA.

RNA – or ribonucleic acid – carries out the instructions coded in DNA, but is also thought to have developed before DNA. Many scientists believe nucleic acids – the 'NA' of 'RNA' – played a key role in the origin of life. A popular theory called the 'RNA World' holds that RNA 'invented' proteins and eventually DNA, but that begs the question, where did RNA come from? Some believe a chemical or biological process gradually evolved an earlier molecule into RNA, while others chalk it up to some kind of non-enzymatic, geochemical reaction. It's a chicken-or-egg debate: what biological process could produce a central building block for life itself? If the process wasn't biological, then what was it and how did it happen?

The new study continues in the tradition of the 1953 Miller–Urey experiment, in which two scientists modeled early-Earth's conditions with a mixture of gases and an electric current to simulate lightning. That experiment yielded amino acids, supporting the idea that biological molecules can spontaneously emerge from non-biological ones in the right circumstances. Despite that finding, the challenge of devising a scenario in which non-biological reactions create RNA has thus far proven insurmountable.

RNA's origins lost in the mists of time

One of the study's authors, biochemist Dr. Nicholas Hud, notes that the many criteria of RNA formation often means that when researchers propose a solution to one problem, a different problem (or two) arises. The links of the RNA chain, which are called nucleotides, are comprised of four bases: adenine (A), cytosine (C), guanine (G) and uracil (U), as well as a phosphate and a ribose sugar. Leslie Orgel, who was a pioneer of the RNA World idea, described the possibility that RNA evolved from an earlier molecule a "gloomy prospect," as it would make solving the origin of RNA harder. The researchers decided it was time to face that challenge.

A re-analysis in 2008 of the Miller–Urey experiment reveals the production of far more non-biological molecules than previously thought, which underpins the authors' hypothesis that molecules necessary for life existed on prebiotic Earth, but because they don't play a major role in life as we now know it, we haven't figured out which molecules or the roles they played all those billions of years ago.

According to Hud, those molecules were "probably very special because the molecules we know of don't behave in ways that indicate they're able to to start life." Those molecules may also contain answers to other questions about life's origins.

The evolution to RNA from an earlier genetic molecule, or proto-RNA, would have been incremental, and each new iteration would have been backward compatible, "like how an updated computer still has to be able to read files from older computers," Hud tells Astrobiology Magazine. Today RNA and DNA use hydrogen-bonded base-pairs to transfer information. Thus, the molecules that don't form the same or similar base-pairs wouldn't have ever worked, leading the researchers to search for "base-pairing molecules that would self-select or segregate themselves on the early Earth into some kind of structure that would help them be incorporated into proto-RNA," says Hud.

New study identifies possible ancestors of RNA
Side-by-side comparison of RNA and DNA for context. Credit: Wikimedia Commons user Sponk

The search for the original molecules

What were those primordial molecules that formed the ancestor of RNA? To determine this, the researchers studied reactions in conditions that mimicked rain and evaporation cycles on the early Earth. After many unsuccessful experiments, they identified three molecular candidates for the bases of proto-RNA: barbituric acid,melamine, and 2, 4, 6-triaminopyrimidine. Reactions with these molecules and the ribose sugar produced nucleosides, which are composite molecules that are close to the sub-units of RNA.

Whereas previous attempts to join the current bases of RNA with ribose in early Earth reactions that were modeled either failed, or produced nucleosides in only very low yields, the researchers measured an 82% nucleoside yield with barbituric acid. Additionally, melamine and the triaminoprymidine molecules spontaneously formed nucleosides in over 50% yields. Dr. Niles Lehman, Professor of Chemistry at Portland State University and Editor-in-Chief of the Journal of Molecular Evolution, believes that the study "provides further support for the RNA World theory by providing a plausible series of events that took nature from chemical chaos to a more defined storage information molecule."

That path isn't completely clear, but it's starting to take shape. According to Hud, their candidates for the ancestral bases of RNA are tantalizingly close to those of modern RNA. However, more needs to happen.

"The molecules we have identified look like they could have functioned in an early genetic system," Hud says. "But we want molecules close enough that you can imagine an evolutionary path where they change into what we have today." While demonstrable plausibility represents a step forward, the question remains whether it's possible to find, and then confirm, the original proto-RNA molecules. Hud acknowledges that while the search might seem daunting, "chemistry is vast, but not infinite. If we accept a few reasonable assumptions about the ancestor of RNA, we can rule out a lot of possibilities. And maybe we can find it." This study represents an important step down that path.

Origins of life elsewhere

Figuring out how RNA formed could help guide the search for extraterrestrial life. "We can gain valuable insight into key problems that need to be overcome for life to arise from non-life," Lehman tells Astrobiology Magazine.

Understanding how life arises could help scientists determine where and how to look for life elsewhere. Amino acids and chemical compounds such as hydrogen cyanide, which has been detected in comets, could give rise to RNA bases, according to Hud. Such a reaction would be "robust, not strange or extraordinary," he says. Similar processes could be underway on other planets and could point to the chemistry scientists should look for when searching for the earliest stages of elsewhere.

Explore further

New Study Brings Scientists Closer to the Origin of RNA

More information: Brian J. Cafferty et al. Searching for Possible Ancestors of RNA: The Self-Assembly Hypothesis for the Origin of Proto-RNA, Prebiotic Chemistry and Chemical Evolution of Nucleic Acids (2018). DOI: 10.1007/978-3-319-93584-3_5

This story is republished courtesy of NASA's Astrobiology Magazine. Explore the Earth and beyond at .

Citation: New study identifies possible ancestors of RNA (2018, September 17) retrieved 19 September 2019 from
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User comments

Sep 17, 2018
Broken Rules of the Hands that Hold Codes

Helicity handed, in deceit departed,
Machinations possessing stability,
Isotropic, when self-embedded,
For the complexity of coordinates,

A genus, to itself, exhibiting indistinguishability,
Timeless entangled, what a degree,
To us, a surface,
A hole or handle, yet to be,

Bits flip, uncaught,
Finite theory's auxiliary,
Metrics for the efficient,
Only to return home with nothing,

Arrival halfway in measure,
Of distance decoupled,
A cancellation in closed,
Best used to see,

As an abuse of the parameter-less,
Inference over orthonormal basis,
Chances are, non-homogeneous
Decays exception, left to error correcting

I do not know what is more fascinating. The our luck with the handedness of electrons, with anthropic transformations, or that unstable RNA would self replicate and eventually modally isolate for semi-permeable configurations

Sep 17, 2018
@spaced - word salad served over a composite of utter nonsense.

Sep 18, 2018
To my mind the CO2 and H2O combines in certain condition to form carbohydrate and similarly Nirogen combines with Hydrogen to form amines to aminoacids and finally protein and these two form RNA and DNA. .

Sep 19, 2018
Life spontaneously coming into existence is about as probable as a tornado ripping through a junkyard and producing a fully functional 747 plane. While it is possible for extremely specific conditions to produce things that are similar to amino acids and rna we are talking about a one in a billion billionths of a chance. And even then that billion billion chance happens, the chance of it happening in an environment that will allow it to exist is another billion billions. If you cant wrap your head around that, just imagine the airplane example above. Is it possible? Yes anything is possible. Is it probable by any wild stretch of the wildest imagination? Not at all.

Here is the rough possibility 4^300. That is: 1 in 4149515568880992958512407863691161151012446232242436899995657330000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000

Sep 19, 2018
Yep! Billions of different biochemical reactions continuously fermenting every minute of energetic sunshine every day for every year over billions of years.

The opportunities for possible self-replicating Azoic prototype lifeforms, eventually adds up to success.

And not a single supernatural drunken bungler in sight!

Sep 19, 2018
The 4^300 probability is well known to be wrong. It's based on an assumption that a very large molecule had to be the first self-replicating molecule. That's not correct. With some Proto-RNA molecules, the odds are 1 in 10^40 - something that could take less than a year (http://www.talkor...rob.html ).

Sep 19, 2018
Additionally, the suggestion that abiogenesis is like a "tornado ripping through a junkyard and producing a fully functional 747 plane" suggests a complete misunderstanding of abiogenesis. Abiogenesis is more like trillions of tornadoes ripping through trillions of junkyards and out of that getting a couple of pieces of a plane formed. Those couple of pieces are able to reproduce and, gradually, over millions of years, more pieces are added until, finally, a 747 is produced.

Sep 20, 2018
Please z6, give credit where credit is due. Tornadoes tearing through junkyards and trailer parks have spawned many of whore trump's voters. Except of course for those provided by pimp putin!

Oct 09, 2018
The 4^300 probability is well known to be wrong. It's based on an assumption that a very large molecule had to be the first self-replicating molecule. That's not correct. With some Proto-RNA molecules, the odds are 1 in 10^40 - something that could take less than a year (http://www.talkor...rob.html ).

It's also based on pure ignorance of what how catalytic proteins function. They have what are known as active sites, often composed of just 4-6 amino acids, where the substrate molecules bind and interact, and replacing one of those few aminos with another can eliminate functionality. But the remaining 294-296 amino acids could survive a huge variety of substitutions that wouldn't affect functionality negatively. In short, a vast number of different 300-amino acid sequences could perform the same job, so calculating the odds of producing just one of these sequences is mental masturbation - easy to do but unproductive.

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