If you thought that the RNA world hypothesis had comfortably eclipsed the DNA world hypothesis, think again. As far as molecular biologists at the MRC Laboratory are concerned, the two hypotheses are in the same orbit—and due to collide. Although the impending clash of ideas may sound catastrophic, it could yield a coherent whole, a mixed RNA–DNA world.

“The RNA world hypothesis suggests that life began with RNA, before a genetic takeover occurred involving primitive biosynthetic machinery and natural selection to result in DNA,” said MRC Laboratory’s John Sutherland, the senior author of a new study that proposes a new cosmology for Earth’s prebiotic chemicals. “Our work suggests that in conditions consistent with shallow primordial ponds and rivulets, there was a mixed genetic system with RNA and DNA building blocks co-existing at the dawn of life. This fulfills what many people think is a key precondition for the spontaneous emergence of life on Earth.”

The new study, titled “Selective prebiotic formation of RNA pyrimidine and DNA purine nucleosides,” appeared June 3 in Nature. It presents the researchers’ idea of a plausible scenario for the primordial Earth’s geochemistry. It also describes how the researchers tested their scenario in the laboratory. To simulate the conditions of a rocky Earth covered with shallow ponds, the researchers dissolved chemicals that form RNA in water, then dried them out and heated them, then they simulated the early sun’s rays by exposing them to ultraviolet radiation.

In this recreation of early Earth geochemistry, intermediates in the synthesis of two of the building blocks of RNA were simultaneously also converted into two of the building blocks of DNA.

“Here we demonstrate a high-yielding, completely stereo-, regio- and furanosyl-selective prebiotic synthesis of the purine deoxyribonucleosides: deoxyadenosine and deoxyinosine,” the authors of the Nature article wrote. “Our synthesis uses key intermediates in the prebiotic synthesis of the canonical pyrimidine ribonucleosides (cytidine and uridine), and we show that, once generated, the pyrimidines persist throughout the synthesis of the purine deoxyribonucleosides, leading to a mixture of deoxyadenosine, deoxyinosine, cytidine, and uridine.”

The current study is the first demonstration that reasonable amounts of a genetic alphabet made up of four building blocks, two for RNA and two for DNA—potentially sufficient to have encoded early life, which was far less complex than life today—may have been available on the primordial Earth. Consequently, the current study challenges one of the leading hypotheses for the advent of life—the RNA world theory, which arose in the 60s and has gained wide acceptance.

The team’s experiments showed that four of the building blocks for DNA and RNA can arise from the same reagents and conditions. They produced cytidine and uridine, two of the building blocks of RNA, and deoxyadenosine, which is one of those of DNA. Deoxyadenosine was partly converted to deoxyinosine, which can take the role of another DNA building block.

These four building blocks, the study’s authors suggest, coexisted before life evolved and were the beginnings of a primitive genetic alphabet. Today, all known living organisms use the same genetic molecules, nucleic acids, to store information. There are two sorts of nucleic acids: DNA and RNA. DNA encodes instructions in genes. Genes are turned into messages using RNA, which carries instructions to make proteins. Proteins can make structures and act as molecular machines.

In the RNA world theory, life started with RNA molecules, which can both store instructions and can act as a modest machine, potentially enabling them to self-replicate. It proposes that through evolution, life in the RNA world gave way to the era of DNA and proteins, because DNA is more stable and durable than RNA.

“The nucleic acids, RNA and DNA, are clearly related,” Sutherland asserted. “This work suggests that they both derive from a hybrid ancestor, rather than one preceding the other.

“Since genetic information always flows from nucleic acids to proteins, and never in reverse—a principle called the ‘central dogma’ of molecular biology by Francis Crick—we now need to uncover how the information which can be stored and purveyed by these nucleic acids could have been first used to make to proteins.”

The chemical origins of life is a fundamental aspect of natural science, and an understanding of these origins could inform the design of future synthetic biology.

“We have demonstrated that co-occurring sequences leading selectively to both RNA pyrimidine and DNA purine nucleosides can result in mixtures that could conceivably complete a genetic alphabet,” the article’s authors concluded. “DNA building blocks can thus be co-produced with the RNA pyrimidine nucleosides—which is consistent with, and perhaps evidence for, the coexistence of RNA and DNA building blocks at the dawn of life.”

“This study shows that blue skies research can reveal fascinating insights into how the very beginnings of life may have emerged, and demonstrates the importance of supporting fundamental research,” said Megan Dowie, head of molecular and cellular medicine at the MRC. “These underpinning discoveries in the life sciences could enable exciting future strategies for artificial biology.”

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