On the Emergence of RNA

Whether there was an RNA world or not, it is indisputable that there was RNA; when, where, and how is yet to be settled. The question of whether “pristine” RNA assembled directly from its components (“prebiotic clutter”), or whether it was a descendant of “simpler” ancestral system(s), is central to the ongoing debate about RNA’s origins. In this review, we look at the facts that suggest RNA is an emergent system and that each component of RNA may have been decided at the level of the oligomer/polymer, and not at the level of the prebiotic clutter, nor at the level of monomer nucleotides. The critical interdependence of RNA’s components – ribofuranose, phosphodiester backbone, and purine-pyrimidine base-pairing – for the functioning of RNA seems to be evident, and manifests itself only at the level of the polymer. Based on the power of such nuanced selections at the polymer level, and coupling it with the reality of the prebiotic mixtures at the monomer level, a scenario is presented wherein the combinatorial interactions of diverse prebiotic (systems) chemistry leads first to chimeric-heterogeneous (aka “pre-RNA”) systems, which can usher in a homogeneous system (RNA), capable of further evolution.     

On the Origin of the Canonical Nucleobases: An Assessment of Selection Pressures across Chemical and Early Biological Evolution

The native bases of RNA and DNA are prominent examples of the narrow selection of organic molecules upon which life is based. How did nature “decide” upon these specific heterocycles? Evidence suggests that many types of heterocycles could have been present on the early Earth. It is therefore likely that the contemporary composition of nucleobases is a result of multiple selection pressures that operated during early chemical and biological evolution. The persistence of the fittest heterocycles in the prebiotic environment towards, for example, hydrolytic and photochemical assaults, may have given some nucleobases a selective advantage for incorporation into the first informational polymers. The prebiotic formation of polymeric nucleic acids employing the native bases remains, however, a challenging problem to reconcile. Hypotheses have proposed that the emerging RNA world may have included many types of nucleobases. This is supported by the extensive utilization of non-canonical nucleobases in extant RNA and the resemblance of many of the modified bases to heterocycles generated in simulated prebiotic chemistry experiments. Selection pressures in the RNA world could have therefore narrowed the composition of the nucleic acid bases. Two such selection pressures may have been related to genetic fidelity and duplex stability. Considering these possible selection criteria, the native bases along with other related heterocycles seem to exhibit a certain level of fitness. We end by discussing the strength of the N-glycosidic bond as a potential fitness parameter in the early DNA world, which may have played a part in the refinement of the alphabetic bases.     

Was a Pyrimidine-Pyrimidine Base Pair the Ancestor of Watson-Crick Base Pairs? Insights from a Systematic Approach to the Origin of RNA

Uncovering the origin of RNA is essential for understanding the origins of life. The persistent inability of chemists to identify a plausible prebiotic route to RNA polymers, along with the seemingly optimal structure of RNA for its functions in extant life, argue in favor of the hypothesis that RNA is a product of chemical or biological evolution. To understand the origin of RNA, we must consider which molecules could have originally acted in place of RNA’s substructures (i.e., nucleobases (the recognition units), ribose (a trifunctional connector), and phosphate (an ionized linker)) in the oldest ancestor of RNA (or proto-RNA). Major challenges to uncovering the chemical structure of proto-RNA include finding molecules that would have spontaneously undergone molecular selection and covalent assembly into an RNA-like polymer, within the complex mixture of the “prebiotic soup” and without the aid of enzymes. In this review, we discuss progress towards identifying the recognition units of proto-RNA and mechanisms by which the ancestral nucleobases might have been originally selected and incorporated into polymers. We consider possible proto-nucleobases within the chemical space of the heterocycles defined by the purines and pyrimidines that have H, NH₂, or O as exocyclic groups (which includes the extant nucleobases). Taking into account the results of numerous experiments that have explored nucleic acids with alternative backbones and noncanonical nucleobases, we are able to remove about half of these 81 molecules from candidacy as ancestral nucleobases. A particularly encouraging result of this approach is the identification of two molecules, 2,4,6-triaminopyrimidine and barbituric acid, which look very promising as possible nucleobases of proto-RNA.     

Prebiotic Origin of Pre-RNA Building Blocks in a Urea “Warm Little Pond” Scenario

Urea appears to be a key intermediate of important prebiotic synthetic pathways. Concentrated pools of urea likely existed on the surface of the early Earth, as urea is synthesized in significant quantities from hydrogen cyanide or cyanamide (widely accepted prebiotic molecules), it has extremely high water solubility, and it can concentrate to form eutectics from aqueous solutions. We propose a model for the origin of a variety of canonical and non-canonical nucleobases, including some known to form supramolecular assemblies that contain Watson-Crick-like base pairs.The dual nucleophilic-electrophilic character of urea makes it an ideal precursor for the formation of nitrogenous heterocycles. We propose a model for the origin of a variety of canonical and noncanonical nucleobases, including some known to form supramolecular assemblies that contain Watson-Crick-like base pairs. These reactions involve urea condensation with other prebiotic molecules (e. g., malonic acid) that could be driven by environmental cycles (e. g., freezing/thawing, drying/wetting). The resulting heterocycle assemblies are compatible with the formation of nucleosides and, possibly, the chemical evolution of molecular precursors to RNA. We show that urea eutectics at moderate temperature represent a robust prebiotic source of nitrogenous heterocycles. The simplicity of these pathways, and their independence from specific or rare geological events, support the idea of urea being of fundamental importance to the prebiotic chemistry that gave rise to life on Earth.     

The Dimeric Proto-Ribosome: Structural Details and Possible Implications on the Origin of Life

A symmetric pocket-like entity, composed of two L-shaped RNA units, encircles the peptide synthesis site within the contemporary ribosome. This entity was suggested to be the vestige of a dimeric proto-ribosome, which could have formed spontaneously in the prebiotic world, catalyzing non-coded peptide bond formation and elongation. This structural element, beyond offering the initial step in the evolution of translation, is hypothesized here to be linked to the origin of life. By catalyzing the production of random peptide chains, the proto-ribosome could have enabled the formation of primary enzymes, launching a process of co-evolution of the translation apparatus and the proteins, thus presenting an alternative to the RNA world hypothesis.     

Prebiotic Organic Chemistry of Formamide and the Origin of Life in Planetary Conditions: What We Know and What Is the Future

The goal of prebiotic chemistry is the depiction of molecular evolution events preceding the emergence of life on Earth or elsewhere in the cosmos. Plausible experimental models require geochemical scenarios and robust chemistry. Today we know that the chemical and physical conditions for life to flourish on Earth were at work much earlier than thought, i.e., earlier than 4.4 billion years ago. In recent years, a geochemical model for the first five hundred million years of the history of our planet has been devised that would work as a cradle for life. Serpentinization processes in the Hadean eon affording self-assembled structures and vesicles provides the link between the catalytic properties of the inorganic environment and the impressive chemical potential of formamide to produce complete panels of organic molecules relevant in pre-genetic and pre-metabolic processes. Based on an interdisciplinary approach, we propose basic transformations connecting geochemistry to the chemistry of formamide, and we hint at the possible extension of this perspective to other worlds.     

An Evolutionary Model Encompassing Substrate Specificity and Reactivity of Type I Polyketide Synthase Thioesterases

Bacterial polyketides are a rich source of chemical diversity and pharmaceutical agents. Understanding the biochemical basis for their biosynthesis and the evolutionary driving force leading to this diversity is essential to take advantage of the enzymes as biocatalysts and to access new chemical diversity for drug discovery. Biochemical characterization of the thioesterase (TE) responsible for 6‐deoxyerythronolide macrocyclization shows that a small, evolutionarily accessible change to the substrate can increase the chemical diversity of products, including macrodiolide formation. We propose an evolutionary model in which TEs are by nature non‐selective for the type of chemistry they catalyze, producing a range of metabolites. As one metabolite becomes essential for improving fitness in a particular environment, the TE evolves to enrich for that corresponding reactivity. This hypothesis is supported by our phylogenetic analysis, showing convergent evolution of macrodiolide‐forming TEs.     

Evolutionary History of Bioessential Elements Can Guide the Search for Life in the Universe

Our understanding of life in the universe comes from one sample, life on Earth. Current and next-generation space missions will target exoplanets as well as planets and moons in our own solar system with the primary goal of detecting, interpreting and characterizing indications of possible biological activity. Thus, understanding life's fundamental characteristics is increasingly critical for detecting and interpreting potential biological signatures elsewhere in the universe. Astrobiologists have outlined the essential roles of carbon and water for life, but we have yet to decipher the rules governing the evolution of how living organisms use bioessential elements. Does the suite of life's essential chemical elements on Earth constitute only one possible evolutionary outcome? Are some elements so essential for biological functions that evolution will select for them despite low availability? How would this play out on other worlds that have different relative element abundances? When we look for life in the universe, or the conditions that could give rise to life, we must learn how to recognize it in extremely different chemical and environmental conditions from those on Earth. We argue that by exposing self-organizing biotic chemistries to different combinations of abiotic materials, and by mapping the evolutionary history of metalloenzyme biochemistry onto geological availabilities of metals, alternative element choices that are very different from life's present-day molecular structure might result. A greater understanding of the paleomolecular evolutionary history of life on Earth will create a predictive capacity for detecting and assessing life's existence on worlds where alternate evolutionary paths might have been taken.     

Trends in chemical engineering education: Process, product and sustainable chemical engineering challenges

Teaching chemical engineering has always been faced with a dilemma: either keep in touch with industry needs or incorporate new scientific concepts into the curriculum. In this paper, a short historical analysis of the evolution of chemical engineering teaching is presented and the recent trends of the two previous facets (industry and science) are briefly reviewed. The process vs product engineering concept is proposed as one of the means to achieve a better alignment between the curriculum and industry needs. A chemical engineering teaching framework, based in part on a product and a process oriented component, which has been in place in our department 5 years ago, is described and discussed. The concept of sustainable chemistry, including process and product considerations, which can be seen as the next frontier in chemical engineering education, is finally analysed from the education point of view.     

RNA dimer synthesis using montmorillonite as a catalyst: The role of surface layer charge

The oligomerisation of activated nucleotides to form RNA is catalyzed by montmorillonite. However, the mechanism of this process and its use as a model for similar prebiotic chemistry is still under investigation. To date, amongst the more than two hundred clay minerals investigated as catalysts, only a few are excellent. We turned our attention to the less efficient catalysts to see how they performed in the synthesis of nucleotide dimers in which a nucleoside and an activated nucleotide produced only linear products of the form MpN. We have found that representative clay minerals, Otay and Chambers specifically, although poor at catalyzing the direct oligomerization of activated nucleotides, are able to promote these dimer syntheses. Sixteen reactions and thirty two products have been studied and found to vary in their outcome. The yields of 2′–5′ and 3′–5′-products were always less than those obtained with the excellent catalyst Volclay®. The results of this research provide a basis for further understanding of the physical processes in the mechanism of this catalysis and suggest that more clay minerals than hitherto expected may have the ability to catalyze RNA synthesis at the dimer level. These results have an important bearing upon the RNA world scenario for the origin of life.     

Prebiotic Pathway from Ribose to RNA Formation

At the focus of abiotic chemical reactions is the synthesis of ribose. No satisfactory explanation was provided as to the missing link between the prebiotic synthesis of ribose and prebiotic RNA (preRNA). Hydrogen cyanide (HCN) is assumed to have been the principal precursor in the prebiotic formation of aldopentoses in the formose reaction and in the synthesis of ribose. Ribose as the best fitting aldopentose became the exclusive sugar component of RNA. The elevated yield of ribose synthesis at higher temperatures and its protection from decomposition could have driven the polymerization of the ribose-phosphate backbone and the coupling of nucleobases to the backbone. RNA could have come into being without the involvement of nucleotide precursors. The first nucleoside monophosphate is likely to have appeared upon the hydrolysis of preRNA contributed by the presence of reactive 2′-OH moieties in the preRNA chain. As a result of phosphorylation, nucleoside monophosphates became nucleoside triphosphates, substrates for the selective synthesis of genRNA.     

Mapping the Conformational Landscape of the Neutral Network of RNA Sequences That Connect Two Functional Distinctly Different Ribozymes

During evolution of an RNA world, the development of enzymatic function was essential. Such enzymatic function was linked to RNA sequences capable of adopting specific RNA folds that possess catalytic pockets to promote catalysis. Within this primordial RNA world, initially evolved self-replicating ribozymes presumably mutated to ribozymes with new functions. Schultes and Bartel (Science 2000 , 289, 448–452) investigated such conversion from one ribozyme to a new ribozyme with distinctly different catalytic functions. Within a neutral network that linked these two prototype ribozymes, a single RNA chain could be identified that exhibited both enzymatic functions. As commented by Schultes and Bartel, this system possessing one sequence with two enzymatic functions serves as a paradigm for an evolutionary system that allows neutral drifts by stepwise mutation from one ribozyme into a different ribozyme without loss of intermittent function. Here, we investigated this complex functional diversification of ancestral ribozymes by analyzing several RNA sequences within this neutral network between two ribozymes with class III ligase activity and with self-cleavage reactivity. We utilized rapid RNA sample preparation for NMR spectroscopic studies together with SHAPE analysis and in-line probing to characterize secondary structure changes within the neutral network. Our investigations allowed delineation of the secondary structure space and by comparison with the previously determined catalytic function allowed correlation of the structure-function relation of ribozyme function in this neutral network.     

Cover Feature: Diamidophosphate (DAP): A Plausible Prebiotic Phosphorylating Reagent with a Chem to BioChem Potential? (ChemBioChem 21/2021)

Known since the 1890s, diamidophosphate (DAP) has been investigated within the context of its inorganic chemistry. In 1999 – with the demonstration of DAP's potential as a phosphorylating agent of sugars in aqueous medium – began the exciting phase of research about DAP's role as a plausible prebiotic phosphorylating agent. More recently, in the last five years, there has been a steady increase in the publications that have documented the surprising versatility of DAP enabling the emergence of many classes of biomolecules of life, such as nucleic acids, peptides and protocells. Thus, though in its infancy, DAP seems to be uniquely positioned to play a central role in modelling abiotic- to prebiotic-chemical evolution. In this context, there is a need for systematic investigations for: (a) establishing DAP's likely availability on the early Earth, and (b) developing DAP's potential as a tool for use in synthetic and bioorganic chemistry.     

高校化学实验教学的绿色化探索

在高校的化学实验教学中,实施绿色化学教学,已经成为了当前教学的必要趋势。绿色化学最本质的特点就是原子经济性,一方面,绿色化学实验可以保证同等的化学效果,另一方面,也不会产生任何污染。由此可见,绿色化学对高校实现可持续发展非常有必要。鉴于此,以高校实施绿色化教学的必要性为出发点,探讨实施绿色化化学实验的措施。     

从化学反应到生命

通过化学进化生成的蛋白质、脂质、三磷酸苷、核糖核酸等,在脂质组成的球膜内,形成具有能量转换、物质传递、并具有遗传性能的个体,是生命最初的形式。作者并指出：弄清楚化学反应的机理。是进一步认识化学进化,生命起源的基础;并将由此引起一场新的工业革命。     

A Step toward Molecular Evolution of RNA: Ribose Binds to Prebiotic Fatty Acid Membranes,and Nucleosides Bind Better than Individual Bases Do

A major challenge in understanding how biological cells arose on the early Earth is explaining how RNA and membranes originally colocalized. We propose that the building blocks of RNA (nucleobases and ribose) bound to self-assembled prebiotic membranes. We have previously demonstrated that the bases bind to membranes composed of a prebiotic fatty acid, but evidence for the binding of sugars has remained a technical challenge. Here, we used pulsed-field gradient NMR spectroscopy to demonstrate that ribose and other sugars bind to membranes of decanoic acid. Moreover, the binding of some bases is strongly enhanced when they are linked to ribose to form a nucleoside or – with the addition of phosphate – a nucleotide. This enhanced binding could have played a role in the molecular evolution leading to the production of RNA.     

Concept of Sustained Ordering and an ATP-related Mechanism of Life’s Origin

This paper shows that the steady state of a system of conjugated reactions, which are characterized by disproportionation of entropy and proceed in the domain of linear interactions, is an attractor of ordering. Such systems are primed to produce ordering, and life is a specific manifestation of the sustained ordering inherent to the chemistry of carbon. The adenosine triphospate (ATP) molecule has properties which makes ATP hydrolysis to be most appropriate to form such a system in primitive world. Hence, ATP is suggested to play a key role in prebiological evolution. Principles of the origin and evolution of life following from the concept of ordering are stated.     

Chance and necessity in the selection of nucleic acid catalysts

In Tom Stoppard's famous play [Rosencrantz and Guildenstern are Dead], the ill-fated heroes toss a coin 101 times. The first 100 times they do so the coin lands heads up. The chance of this happening is approximately 1 in 10(30), a sequence of events so rare that one might argue that it could only happen in such a delightful fiction. Similarly rare events, however, may underlie the origins of biological catalysis. What is the probability that an RNA, DNA, or protein molecule of a given random sequence will display a particular catalytic activity? The answer to this question determines whether a collection of such sequences, such as might result from prebiotic chemistry on the early earth, is extremely likely or unlikely to contain catalytically active molecules, and hence whether the origin of life itself is a virtually inevitable consequence of chemical laws or merely a bizarre fluke. The fact that a priori estimates of this probability, given by otherwise informed chemists and biologists, ranged from 10(-5) to 10(-50), inspired us to begin to address the question experimentally. As it turns out, the chance that a given random sequence RNA molecule will be able to catalyze an RNA polymerase-like phosphoryl transfer reaction is close to 1 in 10(13), rare enough, to be sure, but nevertheless in a range that is comfortably accessible by experiment. It is the purpose of this Account to describe the recent advances in combinatorial biochemistry that have made it possible for us to explore the abundance and diversity of catalysts existing in nucleic acid sequence space.     

Nutzen und Risiken der Chemie

Benefits and risks of chemistry . The benefits of chemistry for mankind are undisputed. Without the discovery and invention of artificial fertilizers the rapidly growing population of the world could not be fed. A fourth of our foodstuffs is currently preserved and improved by crop protection. Besides, an agricultural worker now produces thirty times the amount of agricultural products than was usual fifty years ago. Many developments, such as synthetic fibers and numerous dyes have been made possible only by advances in chemistry; there was a time when dyes were worth their weight in platinum. But what are the risks which chemistry introduces? The basis of chemistry is the conversion of materials. The use of chemical products can lead to interactions with nature, and excessive or uncontrolled usage can in turn endanger life. This biological aspect is the major reason for a wide section of the population being apprehensive about the increasing use of chemical products. An isolated accident involving an explosion leads to a feeling of uncertainty among the populace. One feels that one might be involved oneself at some future date. Thus one of the chief aims in the chemical industry, compared to other branches of industry, is to ensure a very high standard of safety. But the citizen must also be kept well-informed. There is always room for improvement in this direction, and false notions and allegations should be repeatedly corrected. Reasonable legislation which allows chemistry to play its important and positive role in the service of mankind will always be welcomed.     

坚持改革创新的《现代基础化学》第三版教材

《现代基础化学》为工科大一化学的革新教材,我国第一本彩色创绘教材。教材创两段式化学理论教学模式,破传统按周期系论述元素的格局,采取典型元素剖析、以点带面、以少胜多的方法,且辅以展现化学与环境、材料、信息、能源、生命等各科技领域的紧密关联,以及核化学,从而拓展视野,又以科学家轶事启迪人生。经15年坚持改革创新,与时俱进,第三版教材更在削枝强干、化解难点和化学展新上下工夫,使学生具有坚实的化学基础,学会自主学习化学的方法和获取新知的能力。