Discovery means an amazing new view of how life originated on Earth.

The newly described chemical reaction could have assembled DNA building blocks before the existence of life forms and their enzymes.

Discovery promoted the theory that life on our planet originated from RNA-DNA mixtures.

Chemists at Scripps Research have made a discovery that supports a surprising new view of the origin of life on our planet.

In a study published in the journal Chemistry Angevandte Chemi, They demonstrated that a simple compound called dimidophosphate (DAP), which existed on Earth before life, could be chemically woven together into tiny DNA The building block is called deoxynucleosides which are in the strand of primordial DNA.

The discovery is the latest in a series of discoveries over the past several years, pointing to the possibility that DNA and its close chemical cousins Royal army Arose together as products of similar chemical reactions, and that the first self-replicating molecules – the first life forms on Earth – were a mixture of the two.

This discovery may also give rise to new practical applications in chemistry and biology, but its main importance is that it raises the first question of life on Earth. In particular, it paves the way for more comprehensive studies on how self-replicating DNA – RNA mixtures can be developed and spread on primordial Earth and ultimately give priority to the more mature biology of modern organisms.

Senior author Ramnarayan Krishnamurthy, Associate Professor of Chemistry at Scripps Research, says the study, “This discovery is an important step toward the development of a detailed chemical model of how the first life forms originated on Earth.”

This discovery has also taken away the field of basic chemistry from the hypothesis that has dominated it in recent decades: the hypothesis of the “RNA world” states that earlier replicas were RNA-based, and DNA was only a product. Originated later. Of RNA life forms.

Is RNA too sticky?

Krishnamurti and others have doubted the RNA world hypothesis in part because RNA molecules may simply be too “sticky” to serve as the first self-replication.

One edge of RNA can attract other individual RNA building blocks, which stick to form a type of mirror-image strand – each building block in the new strand bound to its complementary building block on the original, “template” strand it happens. If the new strand can detach from the template strand, and by the same process, other new strands can begin to be tempered, then it has achieved the feat of life-reducing self-replication.

But while RNA strands may be good at tempered supplementary strands, they are not so good at separating from these strands. Modern organisms make enzymes that can force dual strands of RNA – or DNA – to go their separate ways, thus enabling replication, but it is unclear how this can be done in the world Where enzymes were not yet present.

A chimeric workaround

Krishnamurthy and his colleagues have shown in recent studies that “chimeric” molecular strands that are part DNA and part RNA may be able to solve this problem, as they can eat complementary strands in a low-viscosity manner that Allows them to be separated relatively easily.

Chemists have shown in widely cited papers over the years that simple ribonucleoside and dexinucleoside building blocks of RNA and DNA, respectively, can originate under very similar chemical conditions on early Earth.

Furthermore, in 2017 they reported that the organic compound DAP may play a key role in modifying ribonucleosides and linking them together in the first RNA strand. The new study suggests that DAP could have done the same for DNA under similar conditions.

“We found, to our surprise, that using DOP works better for reacting with deoxynucleosides when deoxynucleosides are not all the same, but instead different DNA ‘characters such as A and T, or G and C. ‘There are mixtures, such as real DNA, says Eddie Jiménez, first author of a PhD, postdoctoral research associate at Krishnamurthy Lab.

“Now that we better understand how a primordial chemistry could first make RNA and DNA, we can start using it on a mixture of ribonucleoside and deoxynucleoside building blocks to see what chimeric molecules are formed and what. They can self-replicate and develop, ”says Krishnamurthy.

He said that work can also have wide practical applications. Artificial synthesis of DNA and RNA – for example in the “PCR” technique that underlies COVID-19 Testing – volume for a large global business, but depends on enzymes that are relatively fragile and thus have many limitations. Krishnamurthy says that the end of enzyme-free chemical methods to make DNA and RNA may be more attractive.

Reference: “Prebiotic Phosphorylation and Comcomitant Oligomerization of Deoxynucleosides to DNA to Form” Eddy Jiménez, Clementine Gibbard and Ramnarayan Krishnamurthy, 15 December 2020, Angevandte Chemi.
DOI: 10.1002 / aie.202015910

The grant was provided by the Simmons Foundation.

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