With the passage of time, ribose gradually evolved into deoxyribose, RNA was gradually replaced by DNA, and DNA became the genetic material of most organisms. But why is the skeleton of RNA ribose and not other sugars? Some people have tried to explore this question before, but they have not found a simple, universal and effective answer. This problem has never been solved.
At present, there are two schools of thought on this issue. One is the School of Biology. Biologists believe that the first step is not to produce ribose, but to form the original RNA skeleton. According to this school, the original skeleton was gradually replaced by ribose. But the question is why is it replaced by ribose? The specificity of ribose also needs further explanation. This school generally believes that ribose can promote the conformation of RNA.
The second is the School of Chemistry. In 2004, Steven, a famous biochemist and paleogeneticist who was then a professor at the University of Florida? Steven Banner put forward the borate hypothesis for the first time, and related papers were published in the journal Science. He found that ribose can form a relatively stable complex with borate compared with arabinose, xylose and lyxose.
However, the limitation of borate hypothesis is that the reserve of boron in the crust is too low to effectively promote this selection process; The defect of silicate hypothesis is that it cannot be proved that the complex of ribose and silicate is more stable than the other three pentasaccharide complexes. They also have the same problem, that is, the generated valence bond complex is too stable to participate in nucleotide synthesis.
For this difficult problem that few scholars set foot in, Wang Xiao's research group of NTU School of Chemistry and Chemical Engineering chewed up this "hard bone" again. In order to understand this achievement, we must first introduce the glycosylation reaction. Generally speaking, glycosylation reaction is a natural sugar synthesis reaction, which generally starts with formaldehyde molecules and can generate extremely complex monosaccharide or polysaccharide mixture under the action of alkali.
Among them, ribose is not only extremely low in yield, but also extremely unstable in alkaline solution, which means that it cannot exist for a long time, and naturally it is difficult to produce nucleoside. The limitations of the above hypothesis include that they believe that ribose comes from glycosylation. For the borate hypothesis, it is a small probability that borate with very small reserves can meet ribose with very small yield. Chemists constantly improve the glycosylation reaction, trying to increase the yield of ribose, but the results are not ideal.
To this end, Wang Xiao's team put forward a more general new hypothesis. In this work, they jumped out of the bondage of saccharification reaction. Firstly, inspired by modern sugar analysis technology, they studied the retention behavior of various monosaccharides in ion chromatography or ligand exchange chromatography. Through meta-analysis of a large number of literatures in analytical chemistry, fermentation, oceanography and other fields, they found an important phenomenon: ribose has the longest retention time in all monosaccharides.
This is particularly striking. Based on the above phenomenon, they think that the natural selection of ribose in the pre-biological environment is probably determined by the separation process, not by the chemical reaction, and the special properties of ribose are probably determined by its strong coordination with metals.
Ligand exchange chromatography column contains fixed metal ions, because positively charged metal ions attract sugar; Oxygen atoms on sugar like to combine with metal ions, which is called coordination. For other sugars, coordination may not be as strong as ribose. Wang Xiao conceived a material that can adsorb metal ions, which can attract sugar through metal ions, thus enriching ribose. So he thought of clay.
Clay in the earth's crust is very rich, its main component is aluminosilicate, and its major feature is adsorption or exchange of metal ions. Kaolin is the most common clay, and one of its industrial uses is to adsorb heavy metal ions. With clay and metal ions, there is a "natural stationary phase" that can selectively adsorb ribose. Starting from this conjecture, he proposed a model of prehistoric chemistry called "Metal Doped Clay (MDC)".
Based on this assumption, Wang Xiao's team began to test this conjecture with experiments. In their research, they used several clays that can adsorb divalent metals, and studied metals such as divalent copper and ferrous iron. The basis of using divalent metal ions is that a great oxidation event happened on the earth about 2.6 billion years ago (after the birth of primitive life).
At present, it is generally believed that the great oxidation event is caused by cyanobacteria. After the great oxidation event, a lot of oxygen appeared on the earth, and metals can appear in the form of high valence.
At first, Wang Xiao's team investigated four kinds of five-carbon sugars and found that the clay attached to the metal selectively adsorbed ribose, which means that ribose adsorbed the most on it. In addition, they also used density functional theory (DFT) to calculate and simulate the complexes of four pentasaccharide and clay-metal materials, so as to deeply study the special stability of the combination of ribose and clay-metal.
Then, they tested the most common combinations of clay and metal ions, such as kaolin, montmorillonite and mica, and found that most clay-metal materials (MDC) selectively adsorbed R, and extended the experiment to ten mixtures of four-carbon, five-carbon and six-carbon sugars, and found that ribose was still the most abundant on MDC.
In the experiment, they also used an advanced continuous-flow microreactor system, which includes a fixed-bed microreactor, which is a group of very accurate stainless steel modules. They packed MDC material in a micro-fixed bed and used it to simulate the selective adsorption behavior of ribose under water scouring. It was found that MDC could still adsorb more ribose until the end of the flow chemistry experiment. Wang Xiao compared this process to "pillow stone gargling": ribose was adsorbed on clay-metal ("pillow stone") and washed by water flow ("gargling flow") to become the only enriched sugar, thus completing natural selection.
Finally, in order to further verify the MDC model, they tried to add MDC directly into the glycosylation reaction. The results show that ribose is still the most C5-C7 monosaccharide in MDC for complex reaction mixtures.
That is to say, although the yield of ribose in a single glycosylation reaction is limited, ribose can be selectively adsorbed and stabilized on MDC, and finally enriched. For the "downstream reaction", they tested the reactivity of ribose adsorbed by MDC to various bases and found that its activity was no different from that of free ribose.
At the same time, the stability of adsorption of ribose by MDC was tracked, and it was found that the adsorbed ribose still existed at least six weeks later. This shows that the ribose adsorbed by MDC achieves a very good balance between stability and reactivity, and solves these two problems at the same time.
In addition to glycosylation, they also studied nucleoside phosphorylation in the presence of MDC, and found that the yield and 5'- selectivity of the corresponding nucleotide were higher than the reported optimal conditions. In short, after ribose is produced, it will be adsorbed and enriched on clay-metal materials, then glycosylated, then phosphorylated to generate nucleotides, and finally RNA will be formed.
Wang Xiao's team speculated that the earth's environment rich in clay and metal may have been formed from late Archean to early Archean. During this period, a large number of bivalent metal ions brought by hydrothermal fluid interact with ultrabasic rocks on the seabed to produce clay-metal.
Primitive life was born in the early Archean, and this process should not happen again, because since the middle Archean, land appeared and the ocean area decreased, so they speculated that the probability of clay-metal formation also decreased.
On September 23rd, 20021,this work was published in the journal of chemistry, titled "specious pre-biological selection of RNA formation, dynamic separation and nucleotide synthesis based on metal-doped clay". Zhao Zerun, a Ph.D. student of 2020 in NTU School of Chemical Technology, is the first author of the thesis, and Associate Professor Wang Xiao is the correspondent author [1].
This hypothesis is also related to Wang Xiao's chemical accumulation for many years. In 2003, he graduated from the Chemistry Department of Nanjing University with a Bachelor of Science degree. In the same year, he went to the University of Pittsburgh to study under Professor Dennis Curran, a famous organic fluorine chemist, and received his doctorate in 2009. From 2008 to 20 1 1, he conducted postdoctoral research in the laboratory of Professor Stephen Buchwald, an academician of the American Academy of Sciences and MIT. After postdoctoral research, he worked as a lecturer at Harvard Medical School. From 20 17 1 1, he officially returned to Nanjing University to teach.
Talking about the future, Wang Xiao said that in the short term, they will continue to explore various problems in the "RNA world", such as whether the glycosylation reaction of ribose and base can selectively produce N9 purine nucleoside or directly produce pyrimidine nucleoside. At the same time, he stressed that due to the lack of "chemical fossil" evidence, the study of the origin of life is difficult to reach a conclusion, and people can only be infinitely close to the truth. To stand the test, a hypothesis or theory needs to follow several elements besides the core problems it can solve: it conforms to the primitive earth environment, is logical and can conform to modern biology. They will try to do these things.
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Reference:
1. Ze, Xiao Wang, Chemistry 23, (202 1)
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