Discovery of novel primitive xenonucleic acids as alternative genetic polymers adds piece to the origins of life puzzle

The chemical origins of life on Earth is a puzzle scientists have been trying to piece together for decades. Many hypotheses have been proposed to explain how life arose and what chemical and environmental factors were responsible for the early Earth. A required step in many of these hypotheses involves the abiotic synthesis of genetic macromolecules, materials composed of a series of repeating chemical units that have the ability to store and transmit information through base-pair interactions.

One such hypothesis is the RNA (ribonucleic acid) world hypothesis, which derives from this concept and suggests that RNA may have been life’s original biopolymer for catalysis and storage and transmission of genetic information. However, in the absence of chemical activation of RNA monomers, studies have shown that RNA polymerization can be inefficient under pristine dry conditions without special circumstances such as lipid or salt-assisted synthesis or mineral templates.

While this does not necessarily diminish the validity of the RNA world hypothesis, primitive chemical systems were very diverse and likely could not have been clean enough to contain RNA and lipids, suggesting that other forms of primitive nucleic acid polymerization may also have occurred.

One of the leading hypotheses suggests that perhaps another type of nucleic acid called “pre-RNA” may have preceded RNA on early Earth.

Therefore, potentially promising methods to investigate the origin of genetic polymers focus on RNA synthesis under prebiotically plausible conditions, as well as other currently unknown mechanisms for the prebiotic synthesis of non-RNA nucleic acids (or nucleic acid-like polymers). is to investigate. ) could have existed on early Earth, such as copolymerization of linker molecules with monomers of alternating nucleoside analogs.

A team of researchers at the Tokyo Institute of Technology, led by research scientist Ruiqin Yi, worked to investigate these copolymerizations in a non-RNA-based prebiotic-related genetic polymer candidate.

Their latest breakthrough chemical communicationThe team explored the alternating copolymerization of substituted and unsubstituted dicarboxylic acid (DCA) and glycol nucleic acid (GNA) monomers under basic drying conditions to generate linear and branched xenonucleic acid copolymers.

“Studies show that putative pre-RNA molecules can be assembled from monomers with linkers that serve to join potentially other functional polymers to form macromolecular hybrid structures,” said Dr. Yi explains. “This additional chemical interconnection not only increases the complexity of the polymer, but may have given it new functions. Such co-synthesis of polymers could potentially help trace the origins of primitive genetic molecules back to pre-enzyme catalysis or RNA eras. could be.”

To investigate the copolymerizability of the polymer, GNA monomer N^One-(2′,3′-dihydroxypropyl)thymine (DHPT) or N⁹-(2,3-dihydroxypropyl)adenine (DHPA) (including the thymine and adenine bases found in modern DNA and RNA, respectively) reacts with various substituted and unsubstituted DCAs through dehydration synthesis to form An ester bond was formed. GNA components with DCA components.

The synthesized product molecules were subjected to matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF-MS) to analyze the types of products that could potentially be produced. Results revealed that reactions with unsubstituted DCA produced alternating linear copolymers, whereas reactions with substituted DCA produced both linear and branched copolymers. In all cases, the products consisted of polydisperse populations of polymers of different lengths.

Products with different lengths can be obtained by changing the DCA or GNA composition, temperature or reaction pH. When MS/MS analysis was applied to “sequencing” the product polymer, it was found that the DCA/GNA ratio affected the amount of branching in the product. Higher DCA/GNA ratios resulted in more branching, whereas lower ratios resulted in more linear polymers.

Finally, the team also found that a mixed reaction of DHPT and DHPA with 1-tartaric acid forms a randomly ordered polymer composed of two types of bases: thymine and adenine. These products represent a potential pathway for this system to form short-chain polymers capable of carrying genetic information via base pairing, similar to RNA or other primitive nucleic acids.

Thus, the results of this study suggest that the catalog of prebiotic organic molecules, both branched and linear GNA-DCA-based xenonucleic acid copolymers, have diverse compositions and could have been abundant on early Earth if there were simple differences in chemical composition. Branching versus linear information may lead to population-level differences in the abundance of polymers.

For example, branched polymers would have predominated in environments with fewer GNA monomers compared to DCA molecules, which may have been associated with globular protoenzymes based on hyperbranched polymers.

Conversely, environments with more GNA monomers compared to DCA molecules would have dominated a potentially highly diverse population of linear polymers capable of storing and transmitting genetic information, which could lead to further selection and evolution leading to other new functions or nucleic acids. .

“We show that not only can noncanonical xenonucleic acids be formed through simple dehydration of two types of abundant primitive molecules (GNA and DCA), but also that these polymers (containing two types of complementary bases) can hold useful information. We are currently in the process of digging deeper into the potential functions of these copolymers and hope to discover more answers to questions about the types of polymers that could have existed and functioned on the early Earth.” concluded Dr. Lee. .