Newly described chemical reactions can form DNA building blocks before life forms and enzymes exist.
The discovery raises the theory that life on our planet arises from a mixture of RNA-DNA.
The chemists at Scripps Research have found that they support a surprising new view of how life originated on our planet.
In a study published in a journal of chemistry applied Chemistry, they show that a simple compound called diamidophosphate (DAP), which actually existed on Earth before life arose, can be chemically tiny DNA building blocks called deoxynucleosides become primordial DNA strands.
The latest findings in a series of discoveries, a few years ago, indicate the possibility of DNA and its chemical cousins being close RNA arose together as the product of the same chemical reaction, and that the first self-replicating molecule – the first form of life on Earth – is a mixture of the two.
The discovery could also lead to new practical applications in chemistry and biology, but its main importance is to discuss the age question of how life on Earth first emerged. In particular, it paves the way for more extensive research on how copying DNA-RNA mixtures alone can evolve and spread in primordial Earth and ultimately lead to more mature biology for modern organisms.
“This discovery is an important step in developing a detailed chemical model of how life began on Earth,” said senior author who studies Ramanarayanan Krishnamurthy, PhD, associate professor of chemistry at Scripps Research.
The discovery also nudges the chemistry of the origin of life away from the hypotheses that have dominated in the last few decades: The “RNA World” hypothesis suggests that replicas are initially based on RNA, and that DNA rises later to become a product. of RNA life forms.
Why is RNA too close?
Krishnamurthy and others have doubted the RNA World hypothesis in part because RNA molecules are thought to be “too close” to serve as self-replicas.
An RNA strand can attract other individual RNA building blocks, which attach to the shape of a mirror-image strand – each building block on a new strand binds its building block to its original, “template” strand. If the new strand can be separated from the template strand, and, by the same process, start templating another new strand, then it has achieved the achievement of self-replication which is the basis of life.
But while RNA strands can be good for forming complementary strands, they are not very good separate from these strands. Modern organisms produce enzymes that can force twin strands of RNA – or DNA – to separate pathways, allowing for replication, but it is unclear how this can be done in a world where enzymes do not yet exist.
A chimeric solution
Krishnamurthy and colleagues have shown in recent research that “chimeric” molecular strands that are part of DNA and part of RNA are thought to be able to overcome this problem, as they can form complementary strands in a less cohesive way that allows them to separate easily.
Chemists have also shown in a paper frequently quoted in recent years that the simple building blocks of ribonucleosides and deoxynucleoside, from RNA and DNA, could have arisen under very similar conditions on Earth.
Moreover, in 2017 they reported that DAP organic compounds could play an important role in modifying ribonucleosides and making them into the first RNA strands. Recent research suggests that DAP under the same circumstances can do the same for DNA.
“We are surprised that using DAP to react with deoxynucleosides works best when deoxynucleosides are not all the same but a mixture of different DNA ‘letters’ such as A and T, or G and C, such as the original DNA,” said first author Eddy Jiménez, PhD, associated with postdoctoral research in the Krishnamurthy lab.
“Now that we understand how primordial chemistry can create the first RNA and DNA, we can start using a mixture of ribonucleosides and deoxynucleoside building blocks to see what chimeric molecules are formed – and whether they can replicate and evolve,” Krishnamurthy said.
He noted that the job could also have a wide range of practical applications. Synthetic synthesis of DNA and RNA – for example in the basic “PCR” technique COVID-19 tests – the amount to global business is vast, but it depends on relatively fragile enzymes and thus has many limitations. Chemical-free, enzyme-free methods for making DNA and RNA are thought to be more attractive in many contexts, says Krishnamurthy.
References: “Prebiotic Phosphorylation and Concomitant Oligomerization of Deoxynucleosides to Form DNA” by Eddy Jiménez, Clémentine Gibard and Ramanarayanan Krishnamurthy, 15 December 2020, applied Chemistry,
DOI: 10.1002 / anie.202015910
Funding is provided by the Simons Foundation.