Origin of Life Possibly Begins With XNA Before RNA, DNA

A new study explains how DNA-like molecules came from XNAs - xeno nucleic acids - which might be the precursor to the origin of life as we know it.

Researchers from Nagoya University in Japan published the study titled "Nonenzymatic polymerase-like template-directed synthesis of acyclic L-threoninol nucleic acid" in the journal Nature Communications, suggesting a new possibility about how life started. Furthermore, the new model suggested by Japanese researchers has applications in future plans to develop artificial life and biotechnology applications.

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Building the Building Blocks of Life

"The RNA world is widely thought to be a stage in the origin of life," said Keiji Murayama, one of the authors of the study and a biomolecular engineer from Nagoya University. He adds that before the RNA stage, the "pre-RNA world" was most likely based on basic materials called xeno nucleic acids (XNA). Murayama explains that, unlike RNA, it was possible that XNAs replicated even without the use of enzymes. Their research team was able to synthesize a similar XNA, also without enzymes, which further supports the idea that a world of XNAs existed before RNAs did.

Like its supposed successors, an XNA is also formed from chains of nucleotides but with a different sugar backbone. These basic molecules also contain genetic code in a stable manner, mainly because the human body is not capable of degrading them any further. Other studies have reported that XNAs of particular sequences can even act as enzymes themselves, binding to proteins. With this potential, XNAs also has a wide potential in the field of synthetic genetics, biotechnology, and molecular medicine.

Examining the Potential of an XNA World Before DNAs

The Nagoya University research team, led by Hiroyuki Asanuma, wanted to inquire whether the conditions of a young Earth had the right conditions to encourage spontaneous XNA chain formations. To do this, they synthesized acrylic (non-circular) fragments of L-threoninol nucleic acid (L-aTNA), a specific XNA thought to have existed before RNAs. Researchers also made a longer sequence of this L-aTNA using a nucleobase sequence that complemented those of the fragments in similar behavior as DNA strands that match with each other.

When the strands were placed together in a test tube under a controlled environment, the shorter L-aTNA strand came together and connected with each other through the longer L-aTNA sequence, which serves as the template. This linking occurred in the presence of a compound N-cyanomidazole and a metal ion, like manganese - both of which were substances most likely existent during the time of early Earth.

"To the best of our knowledge, this is the first demonstration of template-driven, enzyme-free extension of acyclic XNA from a random fragment pool, generating phosphodiester bonding," Murayama noted.

Researchers were also able to demonstrate that L-aTNA fragments, like the ones they synthesized in their study, could also interlink with DNA and RNA templates, suggesting that the genetic code could be transferred between different materials: from DNA to RNA to L-aTNA and vice versa.

The Nagoya University team is now looking to verify whether an L-aTNA fragment could have been synthesized in the pre-life conditions of an early Earth.

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