RNA-DNA World Circumvents RNA World Sticking Point

Even those who doubt the RNA World hypothesis may find it difficult to argue against it. Consider the plight of a team of scientists at Scripps Research. They suspected that RNA was a weak candidate for the original molecule of self-replication of life chemistry. RNA, they thought, was just too sticky. That is, they believed that complementary RNA strands in the primordial mistletoe would have had difficulty separating because the strand-separating enzymes did not yet exist.

And yet these scientists have discovered that an organic compound called diamidophosphate (DAP) – a compound that may have been present in excess – could have played a crucial role in modifying ribonucleosides and stringing them into the first RNA strands. This finding did not necessarily support the RNA World hypothesis. In fact, it was potentially compatible with the RNA-DNA World hypothesis, which the Scripps Research team considered plausible. But the Scripps Research team has not shown that DAP could do for DNA what it did for RNA.

This deficiency, if it can be called so, has been remedied. In the chemistry journal Angewandte ChemieScripps Research scientists have reported that DAP, together with 2-aminoimidazole, can (amido) phosphorylate and oligomerize deoxynucleosides to form DNA and do so under conditions similar to those of ribonucleosides.

The details appeared on December 15 in a paper entitled “Prebiotic phosphorylation and concomitant oligomerization of deoxynucleosides to form DNA.” The authors of the paper say that their new discovery is the latest in a series of recent discoveries that indicate the possibility that its DNA and nearby chemical RNA appear together as products of similar chemical reactions and that the first self-replicating molecules – the first life forms on Earth – were mixtures of the two.

“Recent demonstrations of RNA-DNA chimeras that allow RNA and DNA replication, together with the prebiotic co-synthesis of deoxyribo- and ribo-nucleotides, have revived the hypothesis of RNA and DNA co-occurrence,” the authors wrote. Combined with previous observations of DAP-mediated chemistry and the constructive role of RNA chimeras, the results reported here help to establish the stage for the systematic investigation of a chemical approach to RNA-DNA coevolution systems.

“Pyrimidine 5′-O-amidophosphates are formed in good yields (~ 60%),” the authors detailed. “Curiously, the presence of pyrimidine nuclei

Although the new paper may lead to new practical applications in chemistry and biology, its main significance is that it addresses the old question of how life first appeared on Earth. In particular, it paves the way for more extensive studies on how DNA-RNA self-replication mixtures could have evolved and spread to primordial Earth, and ultimately sown the more mature biology of modern organisms.

“This discovery is an important step toward developing a detailed chemical model of how the first life forms appeared on Earth,” said Ramanarayanan Krishnamurthy, PhD, lead author and associate professor of chemistry at Scripps Research.

The discovery also pushes the field of chemistry of the origin of life away from the hypothesis that has dominated it in recent decades: the RNA World hypothesis claims that the first replicators were based on RNA and that DNA appeared only later as a product of RNA. . life forms.

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

But while RNA strands may be good at shaping complementary strands, they are not so good at separating these strands. Modern organisms produce enzymes that can force the twinned strands of RNA – or DNA – to go their separate ways, allowing replication, but it is not clear how this could have been done in a world where enzymes did not yet exist.

Krishnamurthy and colleagues have shown in recent studies that “chimeric” molecular strands that are part of DNA and RNA could have solved this problem because they can shape complementary strands in a less sticky way that allows them to separate. relatively easy.

Chemists have also shown in widely cited work in recent years that simple blocks of ribonucleoside and deoxynucleoside, RNA and DNA, respectively, could have appeared under very similar chemical conditions on early Earth.

This line of thinking is encouraged by the current study, which suggests that primary DAP could have been just as useful for DNA as it is for RNA.

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

“Now that we better understand how primordial chemistry could have produced the first RNAs and DNAs, we can start using it on mixtures of ribonucleosides and deoxynucleosides to see what chimeric molecules are formed – and whether they can self-replicate. and evolve, ”Krishnamurthy said.

He added that the work can also have wide practical applications. Artificial DNA and RNA synthesis – for example in the PCR technique underlying COVID-19 testing – amounts to a vast global business, but depends on enzymes that are relatively fragile and therefore have many limitations. Robust, enzyme-free chemical methods to produce DNA and RNA can become more attractive in many contexts, Krishnamurthy suggested.