The RNA-DNA world bypasses the sticking point of the RNA world

Even those who doubt the RNA World hypothesis may find it difficult to argue against it. Consider the predicament facing a team of scientists at Scripps Research. They suspected that RNA was a poor candidate for the original self-replicating molecule in living chemistry. RNA, they thought, was just too sticky. That is, they believed that the complementary RNA strands in the primordial silt would have had a hard time separating because the strand-separating enzymes would not have existed yet.

And yet, these same scientists had discovered that an organic compound called diamidophosphate (DAP) – a compound that could have been present in silt – could have played a crucial role in modifying ribonucleosides and chain them in the first strands of RNA. This finding did not necessarily favor the RNA World hypothesis. In fact, it was potentially consistent with the RNA-DNA world hypothesis, which the Scripps research team found plausible. But the Scripps research team had not shown that DAP can do for DNA what it does for RNA.

This shortcoming, if it can be called that, has been corrected. In the chemistry journal Angewandte Chemie, scientists at Scripps Research reported that DAP, together with 2 – aminoimidazole, can (amido) phosphorylate and oligomerize deoxynucleosides to form DNA under conditions similar to ribonucleosides.

Details were published Dec. 15 in an article titled “Prebiotic Phosphorylation and Concomitant Oligomerization of Deoxynucleosides to Form DNA.” The authors of the article say their new finding is the latest in a series of recent findings pointing to the possibility that DNA and its close chemical cousin, RNA, were born together as products of similar chemical reactions, and that the first self-replicating molecules – the first life formed on Earth – were mixtures of the two.

“Recent demonstrations of RNA-DNA chimeras allowing the replication of RNA and DNA, coupled with the prebiotic co-synthesis of deoxyribonucleotides and ribonucleotides, have resuscitated the hypothesis of the co-emergence of the RNA and DNA, ”wrote the authors of the article. “Combined with previous observations of DAP-mediated chemistries and the constructive role of RDNA chimeras, the findings reported here help set the stage for a systematic investigation of a systems chemistry approach to RNA-DNA coevolution.

“Pyrimidines 5′-O-amidophosphates are formed with good yields (≈60%)”, detail the authors. “Curiously, the presence of pyrimidines nucleos

Although the new work may lead to new practical applications in chemistry and biology, its main significance is that it addresses the age-old question of the birth of life on Earth. In particular, it paves the way for further studies on how self-replicating DNA-RNA mixtures could have evolved and spread on primordial Earth and ultimately sowed the seeds of more mature biology of modern organisms.

“This discovery is an important step towards the development of a detailed chemical model of the origin of the earliest forms of life on Earth,” said Ramanarayanan Krishnamurthy, PhD, lead author of the article and associate professor of chemistry at Scripps Research .

The discovery also takes the field of chemistry away from the origin of life from the hypothesis that has dominated it in recent decades: the RNA world hypothesis assumes that the earliest replicators were based on RNA and DNA did not appear until later as a product of RNA. Life form.

One RNA strand can attract other individual RNA building blocks, which stick to it to form a sort of mirror image strand – each building block in the new strand binding to its complementary building block. on the original “model” strand. If the new strand can detach from the model strand and, in the same process, begin to create other new strands, then it has achieved the feat of self-replication that underlies life.

But while RNA strands can be good at creating complementary strand patterns, they aren’t as good at separating from those strands. Modern organisms make enzymes that can force paired strands of RNA – or DNA – to separate, allowing replication, but it’s unclear how this could have been done in a world where enzymes didn’t exist. not yet.

Krishnamurthy and his colleagues have shown in recent studies that “chimeric” molecular strands that are part of DNA and RNA have been able to bypass this problem, as they can shape complementary strands in a less sticky way that allows them to separate relatively easily. .

Chemists have also shown in widely cited papers in recent years that the simple ribonucleoside and deoxynucleoside building blocks of RNA and DNA, respectively, may have arisen under very similar chemical conditions on early Earth.

This line of thinking is encouraged by the current study, which suggests that primordial DAP could have been as useful to DNA as to RNA.

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

“Now that we have a better understanding of how some primordial chemistry could have produced the first RNA and DNA, we can begin to use it on mixtures of ribonucleosides and deoxynucleosides to see which chimeric molecules are forming – and if they can self-destruct. respond and evolve, ”Krishnamurthy asserted.

He added that the work can also have wide practical applications. Artificial synthesis of DNA and RNA – for example in the PCR technique that underlies COVID-19 testing – represents a vast global activity but depends on relatively fragile enzymes and therefore has many limitations. Robust, enzyme-free chemical methods for making DNA and RNA might end up being more attractive in many settings, Krishnamurthy suggested.

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