Discovery propels the theory that life on Earth originated from an RNA-DNA mix

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

In a study published in the chemistry journal applied chemistry, they showed that a simple compound called diamidophosphate (DAP), believed to have been present on Earth before life originated, could have chemically knitted tiny DNA building blocks called deoxynucleosides into strands of primordial DNA.

The finding is the latest in a series of discoveries in recent years, which indicate that DNA and its closest chemical cousin RNA formed together as products of similar chemical reactions, and that the first self-replicating molecules – the first life form on earth – were mixtures of the two.

The discovery may also lead to new practical applications in chemistry and biology, but its main significance is that it addresses the age-old question of how life on Earth first came to be. In particular, it paves the way for more extensive studies of how self-replicating DNA-RNA mixtures may have evolved and spread across the native Earth, eventually seeding the more mature biology of modern organisms.

“This finding is an important step toward developing a detailed chemical model of how the first life forms on Earth came to be,” said senior author Ramanarayanan Krishnamurthy, Ph.D., associate professor of chemistry at Scripps Research.

The finding also pushes the field of origin of life chemistry away from the hypothesis that has dominated it over the decades: the ‘RNA World’ hypothesis holds that the first replicators were based on RNA and that DNA was only later as a product. arose. of RNA life forms.

Is RNA too sticky?

Krishnamurthy and others have partly questioned the RNA world hypothesis, because RNA molecules were simply too “sticky” to serve as the first self-replicators.

An RNA strand can attract other individual RNA building blocks, which stick to it, forming a kind of mirror-image strand – each building block in the new strand binds to its complementary building block on the original “template” strand. If the new strand can separate from the template strand and, through the same process, can template other new strands, then it has achieved the achievement of self-replication that underlies life.

But while RNA strands are good at templates for complementary strands, they are not so good at separating these strands. Modern organisms make enzymes that can force linked strands of RNA or DNA to go their separate ways, allowing for replication, but it’s unclear how this could have happened in a world where enzymes didn’t yet exist.

A chimeric solution

Krishnamurthy and colleagues have shown in recent studies that “chimeric” molecular strands that are part DNA and part RNA may have circumvented this problem, because they can template complementary strands in a less tacky manner, allowing them to separate relatively easily. .

The chemists have also shown in much-cited papers in recent years that the simple ribonucleoside and deoxynucleoside building blocks, of RNA and DNA, respectively, could have originated under very similar chemical conditions on the early Earth.

In addition, they reported in 2017 that the organic compound DAP could have played the critical role of modifying ribonucleosides and stringing them together to form the first RNA strands. The new study shows that under similar circumstances, DAP could have done the same for DNA.

“We found to our surprise that using DAP to react with deoxynucleosides works better when the deoxynucleosides are not all the same, but are instead mixtures of different DNA ‘letters’ such as A and T, or G and C, such as real DNA, ”says lead author Eddy Jiménez, Ph.D., a postdoctoral research associate in the Krishnamurthy laboratory.

Now that we better understand how a primordial chemistry could have made the first RNAs and DNAs, we can start using it on mixtures of ribonucleoside and deoxynucleoside building blocks to see which chimeric molecules are formed – and whether they can replicate and evolve themselves, ” Krishnamurthy says.

He notes that the work can also have broad practical applications. The artificial synthesis of DNA and RNA – for example in the “PCR” technique that underlies COVID-19 assays – represents a huge global business, but relies on enzymes that are relatively fragile and thus have many limitations. Robust, enzyme-free chemical methods for making DNA and RNA can become more attractive in many contexts, Krishnamurthy says.