The chemical origin of life on Earth has been a subject of interest for scientists for several decades. Various hypotheses have been proposed to explain how life originated and what environmental and chemical factors contributed to it. One of the crucial steps in many of these hypotheses involves the abiotic synthesis of genetic polymers, which are materials that can store and transmit information through base-pairing interactions. RNA (ribonucleic acid) World Hypothesis is one such theory that suggests RNA was the original biopolymer of life for genetic information storage and transmission as well as catalysis. However, studies have found that RNA polymerization under primitive dry-down conditions would have been inefficient without specialized circumstances such as lipid or salt-assisted synthesis or mineral templating. This has led scientists to explore other forms of primitive nucleic acid polymerization that may have taken place, such as the co-polymerization of monomers of alternating nucleoside analogs with linker molecules.
Research Findings
A team of researchers from Tokyo Institute of Technology led by Research Scientist Ruiqin Yi examined co-polymerizations in a non-RNA-based prebiotically relevant genetic polymer candidate to investigate the origins of genetic polymers. The team explored alternating co-polymerization of glycol nucleic acid (GNA) monomers with substituted and unsubstituted dicarboxylic acids (DCA) under primitive dry-down conditions to produce both linear and branched xeno nucleic acid co-polymers. The team found that putative pre-RNA molecules could be assembled from monomers with linkers that potentially served to conjoin other functional polymers to form macromolecular hybrid structures. This additional chemical interconnectivity not only increases the complexity of the polymers but also may have imparted them with novel or emergent functions. Such polymer co-synthesis can potentially help trace the origin of primitive genetic molecules back to an era before enzymatic catalysis or RNA.
To investigate the co-synthesis of polymers, GNA monomers N1-(2′,3′- dihydroxypropyl)thymine (DHPT) or N9-(2,3-dihydroxypropyl)adenine (DHPA) were reacted with a range of substituted and unsubstituted DCAs via dehydration synthesis to form ester bonds capable of connecting the GNA components with the DCA components. The synthesized product molecules were then 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. The results revealed that reactions with unsubstituted DCAs produced alternating linear co-polymers, while the ones with substituted DCAs produced both linear and branched co-polymers; in all cases, the products were composed of a polydisperse population of polymers of different lengths.
By varying the DCA or GNA composition, temperature, or reaction pH, products of different lengths could be obtained. When MS/MS analysis was applied to “sequence” the product polymers, it was revealed that the DCA/GNA ratio affected the amount of branching of the products; higher DCA/GNA ratios resulted in more branching, while lower ratios resulted in more linear polymers. The mixed reaction of DHPT and DHPA with ʟ-tartaric acid led to the formation of a random sequence of polymers consisting of both types of bases, which themselves can typically base-pair. These products indicate a potential pathway for this system to form short-chained polymers capable of genetic information transmission via base-pairing, similar to RNA or other primitive nucleic acids.
The results of the research suggest that both branched and linear GNA–DCA-based xeno nucleic acid co-polymers might have been abundant on early Earth if the inventory of prebiotic organic molecules had a diverse composition. Simple differences in the chemical composition could have led to population-level differences in the abundance of branched vs. linear informational polymers. The team found that not only could non-canonical xeno nucleic acids be formed through simple dehydration of two types of abundant primitive molecules (GNA and DCA), but also that these polymers could have had useful information storage properties. Thus, this research provides a potentially promising way of investigating the origins of genetic polymers by exploring other currently unknown mechanisms of prebiotic synthesis of non-RNA nucleic acids, such as co-polymerization of monomers of alternating nucleoside analogs with linker molecules. The team is now in the process of diving deeper into the potential functions of these co-polymers to uncover more answers about the types of polymers that could have existed and functioned on early Earth.
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