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1.
Nucleic Acids Res ; 49(2): 646-656, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33347562

RESUMO

The prebiotic synthesis of ribonucleotides is likely to have been accompanied by the synthesis of noncanonical nucleotides including the threo-nucleotide building blocks of TNA. Here, we examine the ability of activated threo-nucleotides to participate in nonenzymatic template-directed polymerization. We find that primer extension by multiple sequential threo-nucleotide monomers is strongly disfavored relative to ribo-nucleotides. Kinetic, NMR and crystallographic studies suggest that this is due in part to the slow formation of the imidazolium-bridged TNA dinucleotide intermediate in primer extension, and in part because of the greater distance between the attacking RNA primer 3'-hydroxyl and the phosphate of the incoming threo-nucleotide intermediate. Even a single activated threo-nucleotide in the presence of an activated downstream RNA oligonucleotide is added to the primer 10-fold more slowly than an activated ribonucleotide. In contrast, a single activated threo-nucleotide at the end of an RNA primer or in an RNA template results in only a modest decrease in the rate of primer extension, consistent with the minor and local structural distortions revealed by crystal structures. Our results are consistent with a model in which heterogeneous primordial oligonucleotides would, through cycles of replication, have given rise to increasingly homogeneous RNA strands.


Assuntos
Moldes Genéticos , Tetroses/química , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Origem da Vida , Polimerização , RNA/química , Relação Estrutura-Atividade
2.
Science ; 370(6518): 767-768, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33184194
3.
Adv Genet ; 106: 1-4, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33081918

RESUMO

This current volume is, in many ways, a 2020 update to the important 1999-2000 compendium by Sir Fred Hoyle and Professor N. Chandra Wickramasinghe's "Astronomical Origins of life: Steps towards Panspermia." The emerging new paradigm of biology that connects life on Earth with the wider cosmos is covered in considerable depth showing that terrestrial biological evolution is best understood as a cosmically derived habitat and an interconnected genetic system. The various chapters here discuss all aspects of this interconnectedness, particularly relevant now in this time of the coronavirus pandemic (COVID-19) as the human race reacts to the many microbes and viral pathogens that arrive regularly from space.


Assuntos
Evolução Biológica , Meio Ambiente , Exobiologia , Interações Hospedeiro-Patógeno/fisiologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Doença/etiologia , Ecossistema , Meio Ambiente Extraterreno , Humanos , Modelos Biológicos , Origem da Vida , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia
4.
Adv Genet ; 106: 75-100, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33081928

RESUMO

The origins and global spread of two recent, yet quite different, pandemic diseases is discussed and reviewed in depth: Candida auris, a eukaryotic fungal disease, and COVID-19 (SARS-CoV-2), a positive strand RNA viral respiratory disease. Both these diseases display highly distinctive patterns of sudden emergence and global spread, which are not easy to understand by conventional epidemiological analysis based on simple infection-driven human- to-human spread of an infectious disease (assumed to jump suddenly and thus genetically, from an animal reservoir). Both these enigmatic diseases make sense however under a Panspermia in-fall model and the evidence consistent with such a model is critically reviewed.


Assuntos
Evolução Biológica , Candidíase/etiologia , Doenças Transmissíveis Emergentes/etiologia , Infecções por Coronavirus/etiologia , Origem da Vida , Pneumonia Viral/etiologia , Animais , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Candida/isolamento & purificação , Candida/fisiologia , Candidíase/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Coronavirus/isolamento & purificação , Coronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Planeta Terra , Exobiologia , Meio Ambiente Extraterreno , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia
5.
Proc Natl Acad Sci U S A ; 117(41): 25230-25236, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-32989134

RESUMO

Autocatalysis is essential for the origin of life and chemical evolution. However, the lack of a unified framework so far prevents a systematic study of autocatalysis. Here, we derive, from basic principles, general stoichiometric conditions for catalysis and autocatalysis in chemical reaction networks. This allows for a classification of minimal autocatalytic motifs called cores. While all known autocatalytic systems indeed contain minimal motifs, the classification also reveals hitherto unidentified motifs. We further examine conditions for kinetic viability of such networks, which depends on the autocatalytic motifs they contain and is notably increased by internal catalytic cycles. Finally, we show how this framework extends the range of conceivable autocatalytic systems, by applying our stoichiometric and kinetic analysis to autocatalysis emerging from coupled compartments. The unified approach to autocatalysis presented in this work lays a foundation toward the building of a systems-level theory of chemical evolution.


Assuntos
Evolução Química , Modelos Químicos , Origem da Vida , Catálise , Cinética
6.
Proc Natl Acad Sci U S A ; 117(35): 21031-21036, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32817511

RESUMO

One of the major goals for astronomy in the next decades is the remote search for biosignatures (i.e., the spectroscopic evidence of biological activity) in exoplanets. Here we adopt a Bayesian statistical framework to discuss the implications of such future searches, both in the case when life is detected and when no definite evidence is found. We show that even a single detection of biosignatures in the vicinity of our stellar system, in a survey of similar size to what will be obtainable in the next 2 decades, would affect significantly our prior belief on the frequency of life in the universe, even starting from a neutral or pessimistic stance. In particular, after such discovery, an initially agnostic observer would be led to conclude that there are more than [Formula: see text] inhabited planets in the galaxy with a probability exceeding 95%. However, this conclusion would be somewhat weakened by the viability of transfer of biological material over interstellar distances, as in panspermia scenarios. Conversely, the lack of significant evidence of biosignatures would have little effect, leaving the assessment of the abundance of life in the galaxy still largely undetermined.


Assuntos
Exobiologia/métodos , Análise Espectral/métodos , Astronomia , Teorema de Bayes , Meio Ambiente Extraterreno , Galáxias , Origem da Vida , Planetas
7.
PLoS One ; 15(8): e0238253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857812

RESUMO

The origins of life on Earth have been the subject of inquiry since the early days of philosophical thought and are still intensively investigated by the researchers around the world. One of the theories explaining the life emergence, that gained the most attention recently is the RNA World hypothesis, which assumes that life on Earth was sparked by replicating RNA chains. Since wet lab analysis is time-consuming, many mathematical and computational approaches have been proposed that try to explain the origins of life. Recently proposed one, based on the work by Takeuchi and Hogeweg, addresses the problem of interplay between RNA replicases and RNA parasitic species, which is crucial for understanding the first steps of prebiotic evolution. In this paper, the aforementioned model has been extended and modified by introducing RNA sequence (structure) information and mutation rate close to real one. It allowed to observe the simple evolution mechanisms, which could have led to the more complicated systems and eventually, to the formation of the first cells. The main goal of this study was to determine the conditions that allowed the spontaneous emergence and evolution of the prebiotic replicases equipped with simple functional domains within a large population. Here we show that polymerase ribozymes could have appeared randomly and then quickly started to copy themselves in order for the system to reach equilibrium. It has been shown that evolutionary selection works even in the simplest systems.


Assuntos
Sequência de Bases , Simulação por Computador , Modelos Teóricos , Conformação de Ácido Nucleico , Origem da Vida , RNA , Algoritmos , Difusão , Hidrólise , Mutação , RNA/química , /genética
8.
PLoS One ; 15(7): e0235808, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32722674

RESUMO

One of the central aims of synthetic biology (SB) is to better understand the mechanisms of life by trying to develop and synthesize new forms and perhaps modes of life. While the question of what is life has occupied mankind for centuries, there is a lack of empirical research examining the basic concepts of life scientists within SB themselves refer to and build on. In order to gain insights into these fundamental concepts, we conducted a qualitative interview study with scientists working in the field of SB. The aim was to gain a better understanding of the underlying understandings, principles, and characteristics of (synthetic) life on the one hand, and the entangled consequences for the conducted experiments and studies as well as the pursued scientific approaches. We identified four primarily underlying basic concepts of life which serve as a fundamental framework for current and further scientific research within SB and have implications for research questions, approaches and aims as well as for the evaluation of scientific results.


Assuntos
Biomimética , Biologia Sintética , Biomimética/métodos , Compreensão , Feminino , Humanos , Masculino , Origem da Vida , Pesquisa , Pesquisadores , Biologia Sintética/métodos
9.
Proc Natl Acad Sci U S A ; 117(24): 13267-13274, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32487725

RESUMO

Continuous reaction networks, which do not rely on purification or timely additions of reagents, serve as models for chemical evolution and have been demonstrated for compounds thought to have played important roles for the origins of life such as amino acids, hydroxy acids, and sugars. Step-by-step chemical protocols for ribonucleotide synthesis are known, but demonstrating their synthesis in the context of continuous reaction networks remains a major challenge. Herein, compounds proposed to be important for prebiotic RNA synthesis, including glycolaldehyde, cyanamide, 2-aminooxazole, and 2-aminoimidazole, are generated from a continuous reaction network, starting from an aqueous mixture of NaCl, NH4Cl, phosphate, and HCN as the only carbon source. No well-timed addition of any other reagents is required. The reaction network is driven by a combination of γ radiolysis and dry-down. γ Radiolysis results in a complex mixture of organics, including the glycolaldehyde-derived glyceronitrile and cyanamide. This mixture is then dried down, generating free glycolaldehyde that then reacts with cyanamide/NH3 to furnish a combination of 2-aminooxazole and 2-aminoimidazole. This continuous reaction network models how precursors for generating RNA and other classes of compounds may arise spontaneously from a complex mixture that originates from simple reagents.


Assuntos
Evolução Química , Modelos Químicos , RNA/química , RNA/síntese química , Acetaldeído/análogos & derivados , Acetaldeído/síntese química , Acetaldeído/química , Cianamida/síntese química , Cianamida/química , Raios gama , Imidazóis/síntese química , Imidazóis/química , Origem da Vida , Oxazóis/síntese química , Oxazóis/química , Fotoquímica , Água/química
10.
Nat Commun ; 11(1): 3137, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561731

RESUMO

The close synergy between peptides and nucleic acids in current biology is suggestive of a functional co-evolution between the two polymers. Here we show that cationic proto-peptides (depsipeptides and polyesters), either produced as mixtures from plausibly prebiotic dry-down reactions or synthetically prepared in pure form, can engage in direct interactions with RNA resulting in mutual stabilization. Cationic proto-peptides significantly increase the thermal stability of folded RNA structures. In turn, RNA increases the lifetime of a depsipeptide by >30-fold. Proto-peptides containing the proteinaceous amino acids Lys, Arg, or His adjacent to backbone ester bonds generally promote RNA duplex thermal stability to a greater magnitude than do analogous sequences containing non-proteinaceous residues. Our findings support a model in which tightly-intertwined biological dependencies of RNA and protein reflect a long co-evolutionary history that began with rudimentary, mutually-stabilizing interactions at early stages of polypeptide and nucleic acid co-existence.


Assuntos
Evolução Molecular , Peptídeos/metabolismo , Dobramento de Proteína , Estabilidade de RNA , RNA/metabolismo , Sequência de Aminoácidos , Aminobutiratos/química , Aminobutiratos/metabolismo , Cátions/química , Cátions/metabolismo , Dicroísmo Circular , Hidrólise , Ressonância Magnética Nuclear Biomolecular , Origem da Vida , Ornitina/química , Ornitina/metabolismo , Peptídeos/química , Estabilidade Proteica , RNA/química , beta-Alanina/análogos & derivados , beta-Alanina/química , beta-Alanina/metabolismo
11.
Nature ; 582(7810): 60-66, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32494078

RESUMO

The nature of the first genetic polymer is the subject of major debate1. Although the 'RNA world' theory suggests that RNA was the first replicable information carrier of the prebiotic era-that is, prior to the dawn of life2,3-other evidence implies that life may have started with a heterogeneous nucleic acid genetic system that included both RNA and DNA4. Such a theory streamlines the eventual 'genetic takeover' of homogeneous DNA from RNA as the principal information-storage molecule, but requires a selective abiotic synthesis of both RNA and DNA building blocks in the same local primordial geochemical scenario. Here we demonstrate a high-yielding, completely stereo-, regio- and furanosyl-selective prebiotic synthesis of the purine deoxyribonucleosides: deoxyadenosine and deoxyinosine. Our synthesis uses key intermediates in the prebiotic synthesis of the canonical pyrimidine ribonucleosides (cytidine and uridine), and we show that, once generated, the pyrimidines persist throughout the synthesis of the purine deoxyribonucleosides, leading to a mixture of deoxyadenosine, deoxyinosine, cytidine and uridine. These results support the notion that purine deoxyribonucleosides and pyrimidine ribonucleosides may have coexisted before the emergence of life5.


Assuntos
DNA/química , Evolução Química , Origem da Vida , Nucleosídeos de Purina/síntese química , Nucleosídeos de Pirimidina/síntese química , RNA/química , Adenosina/análogos & derivados , Adenosina/química , Citidina/química , DNA/genética , Oxirredução/efeitos da radiação , Nucleosídeos de Purina/química , Nucleosídeos de Purina/genética , Nucleosídeos de Pirimidina/química , Nucleosídeos de Pirimidina/genética , RNA/genética , Uridina/química
13.
NPJ Syst Biol Appl ; 6(1): 12, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376854

RESUMO

The genomic platform that informs evolution of microRNA cascades remains unknown. Here we capitalised on the recent evolutionary trajectory of hominin-specific miRNA-4673, encoded in intron 4 of notch-1, to uncover the identity of one such precursor genomic element and the selective forces acting upon it. The miRNA targets genes that regulate Wnt/ß-catenin signalling cascade. Primary sequence of the microRNA and its target region in Wnt modulating genes evolved from homologous signatures mapped to homotypic cis-clusters recognised by TCF3/4 and TFAP2A/B/C families. Integration of homologous TFAP2A/B/C cis-clusters (short range inhibitor of ß-catenin) into the transcriptional landscape of Wnt cascade genes can reduce noise in gene expression. Probabilistic adoption of miRNA secondary structure by one such cis-signature in notch-1 reflected selection for superhelical curvature symmetry of precursor DNA to localise a nucleosome that overlapped the latter cis-cluster. By replicating the cis-cluster signature, non-random interactions of the miRNA with key Wnt modulator genes expanded the transcriptional noise buffering capacity via a coherent feed-forward loop mechanism. In consequence, an autonomous transcriptional noise dampener (the cis-cluster/nucleosome) evolved into a post-transcriptional one (the miRNA). The findings suggest a latent potential for remodelling of transcriptional landscape by miRNAs that capitalise on non-random distribution of genomic cis-signatures.


Assuntos
MicroRNAs/genética , MicroRNAs/metabolismo , Expressão Gênica , Redes Reguladoras de Genes , Genoma , Genômica , Humanos , Origem da Vida , Receptor Notch1/genética , Via de Sinalização Wnt/genética , beta Catenina
14.
Nucleic Acids Res ; 48(12): e70, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32427335

RESUMO

Life emerging in an RNA world is expected to propagate RNA as hereditary information, requiring some form of primitive replication without enzymes. Non-enzymatic template-directed RNA primer extension is a model of the copying step in this posited form of replication. The sequence space accessed by primer extension dictates potential pathways to self-replication and, eventually, ribozymes. Which sequences can be accessed? What is the fidelity of the reaction? Does the recently illuminated mechanism of primer extension affect the distribution of sequences that can be copied? How do sequence features respond to experimental conditions and prebiotically relevant contexts? To help answer these and related questions, we here introduce a deep-sequencing methodology for studying RNA primer extension. We have designed and vetted special RNA constructs for this purpose, honed a protocol for sample preparation and developed custom software that analyzes sequencing data. We apply this new methodology to proof-of-concept controls, and demonstrate that it works as expected and reports on key features of the sequences accessed by primer extension.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , RNA-Seq/métodos , Software , Primers do DNA/química , Primers do DNA/genética , Origem da Vida , RNA/química , RNA/genética
15.
Proc Natl Acad Sci U S A ; 117(22): 11995-12003, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32424083

RESUMO

Life emerged on Earth within the first quintile of its habitable window, but a technological civilization did not blossom until its last. Efforts to infer the rate of abiogenesis, based on its early emergence, are frustrated by the selection effect that if the evolution of intelligence is a slow process, then life's early start may simply be a prerequisite to our existence, rather than useful evidence for optimism. In this work, we interpret the chronology of these two events in a Bayesian framework, extending upon previous work by considering that the evolutionary timescale is itself an unknown that needs to be jointly inferred, rather than fiducially set. We further adopt an objective Bayesian approach, such that our results would be agreed upon even by those using wildly different priors for the rates of abiogenesis and evolution-common points of contention for this problem. It is then shown that the earliest microfossil evidence for life indicates that the rate of abiogenesis is at least 2.8 times more likely to be a typically rapid process, rather than a slow one. This modest limiting Bayes factor rises to 8.7 if we accept the more disputed evidence of 13C-depleted zircon deposits [E. A. Bell, P. Boehnke, T. M. Harrison, W. L. Mao, Proc. Natl. Acad. Sci. U.S.A. 112, 14518-14521 (2015)]. For intelligence evolution, it is found that a rare-intelligence scenario is slightly favored at 3:2 betting odds. Thus, if we reran Earth's clock, one should statistically favor life to frequently reemerge, but intelligence may not be as inevitable.


Assuntos
Exobiologia , Origem da Vida , Teorema de Bayes , Evolução Biológica , Planeta Terra , Exobiologia/métodos , Exobiologia/estatística & dados numéricos , Inteligência
16.
Nat Commun ; 11(1): 2192, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366844

RESUMO

Major evolutionary transitions, including the emergence of life, likely occurred in aqueous environments. While the role of water's chemistry in early life is well studied, the effects of water's ability to manipulate population structure are less clear. Population structure is known to be critical, as effective replicators must be insulated from parasites. Here, we propose that turbulent coherent structures, long-lasting flow patterns which trap particles, may serve many of the properties associated with compartments - collocalization, division, and merging - which are commonly thought to play a key role in the origins of life and other evolutionary transitions. We substantiate this idea by simulating multiple proposed metabolisms for early life in a simple model of a turbulent flow, and find that balancing the turnover times of biological particles and coherent structures can indeed enhance the likelihood of these metabolisms overcoming extinction either via parasitism or via a lack of metabolic support. Our results suggest that group selection models may be applicable with fewer physical and chemical constraints than previously thought, and apply much more widely in aqueous environments.


Assuntos
Algoritmos , Hidrodinâmica , Modelos Teóricos , Água/química , Evolução Biológica , Fenômenos Biofísicos , Difusão , Movimento (Física) , Origem da Vida , Reologia , Viscosidade , Água/metabolismo
17.
Trends Ecol Evol ; 35(5): 397-406, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32294421

RESUMO

Evolution requires self-replication. But, what was the very first self-replicator directly ancestral to all life? The currently favoured RNA World theory assigns this role to RNA alone but suffers from a number of seemingly intractable problems. Instead, we suggest that the self-replicator consisted of both peptides and nucleic acid strands. Such a nucleopeptide replicator is more feasible both in the light of the replication machinery currently found in cells and the complexity of the evolutionary path required to reach them. Recent theoretical and mathematical work supports this idea and provide a blueprint for future investigations.


Assuntos
Origem da Vida , RNA , Peptídeos/genética , RNA/genética
18.
J Phys Chem A ; 124(20): 4150-4159, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32348131

RESUMO

The emergence of life on the prebiotic Earth must have involved the formation of polypeptides, yet the polymerization of amino acids is thermodynamically unfavorable under biologically relevant aqueous conditions because amino acids are zwitterions in solution and because of the production of a water molecule through a condensation reaction. Many mechanisms for overcoming this thermodynamic unfavorability have been proposed, but the role of gas phase water clusters has not been investigated. We present the thermodynamics of the water-mediated gas phase dimerization reaction of glycine as a model for the atmospheric polymerization of amino acids prior to the emergence of biological machinery. We hypothesize that atmospheric aerosols may have played a major role in the prebiotic formation of peptide bonds by providing the thermodynamic driving force to facilitate increasingly stable linear oligopeptides. In addition, we hypothesize that small aerosols orient amino acids on their surfaces, thus providing the correct molecular orientations to funnel the reaction pathways of peptides through transition states that lead eventually to polypeptide products. Using density functional theory and a thorough configurational sampling technique, we show that the thermodynamic spontaneity of the linear dimerization of glycine in the gas phase can be driven by the addition of individual water molecules.


Assuntos
Evolução Química , Gases/química , Origem da Vida , Peptídeos/química , Água/química , Sítios de Ligação , Dimerização , Glicina/química , Cinética , Modelos Moleculares , Prebióticos , Termodinâmica
20.
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