Depuis la découverte de la chiralité moléculaire par Pasteur il y a plus de 150 ans, l'origine de l'homochiralité de la vie reste un mystère non résolu et troublant, qui remonte probablement à l'origine de la vie elle-même. Cette énigme a récemment été recensée dans Nature comme étant l’une des cinq plus grandes énigmes non résolues par la science.Aujourd'hui il existe deux façons d’aborder le problème de l'origine de l'asymétrie moléculaire impliquant des scénarios soit déterministes soit aléatoires. Ces derniers étant basés sur la résolution spontanée des énantiomères, et sont donc impossible à tester. En revanche, les théories déterministes peuvent être confrontées à l’expérience afin notamment de valider la reproductibilité de leur influence chirale.Le présent manuscrit est une synthèse bibliographique et expérimentale mettant en évidence les interactions de la LPC avec des molécules chirales dans le cadre de l’origine de l’homochiralité de la vie. Ces travaux ont pour but de mieux comprendre les propriétés chiroptiques de molécules chirales ainsi que de déterminer les espèces chirales susceptibles d'être présentes dans la glace cométaire / Since the Pasteur’s discovery of chirality more than 150 years ago, the origin of homochirality remains to be an unresolved mystery, which is probably linked to the origin of life-itself. This puzzle was named by the journal Nature as one of the five biggest unresolved puzzles in modern science.Today there exist two ways to address the question of the origin of molecular homochirality. It implies either deterministic or chance scenario. The latest is based on the spontaneous resolution of enantiomers by phase transition, and in consequence, it cannot be tested. On the other hand, deterministic theories can be subjected to experimental confirmation, since if there was, in fact, a chiral influence that imposed its chirality this should in principle be reproducible.The presented manuscript is a synthesis of bibliographic research and experimental studies that focus on the interaction of CPL with chiral molecules which are put in the context of the origin of homochirality of life. This work is aiming to advance our understanding of chiroptical properties of chiral molecules as well as to determine chiral species susceptible to be present in cometary ice

Nickel enzymes have been suggested, through numerous phylogenetic studies, to have been among the very first catalytic compounds on the early Earth, possibly present in the last universal common ancestor (LUCA) or prior to the onset of life. This is because of the type of reactions catalyzed by some of these enzymes, the nature of organisms that utilize them, their distribution in the tree of life, and their key roles in what is now thought of as possibly one of the oldest carbon fixation pathways, the Wood-Ljungdahl (WL) pathway. Additionally, nickel is generally thought to have been an abundant element on the early Earth, highly soluble in what were, theoretically, euxinic (anoxic and sulfidic) ocean waters. This combined with the fact that the enzymes involved in the WL pathway have an active center configuration that resembles that of minerals found in hydrothermal vent walls, makes nickel enzymes a likely candidate to have evolved from what were proto-enzymes, responsible for the prebiotic catalysis of the first simple organic molecules prior to the origins of life, according to the so-called submarine alkaline hydrothermal vent theory, first presented by Michael J. Russell in 1993 (Russell et al. 1994). In this study, I expand the known coverage on the distribution of these enzymes by mapping them in 10,575 OTUs of microbial taxa. Using their pattern of distribution, I reconstruct their histories along the branches of a reference phylogenetic tree of the same taxa through methods of ancestral reconstruction of discrete traits. Additionally, I construct an individual gene tree for each of the enzymes in order to consolidate gene history with species history. My results showed that the redox nickel enzymes (except methyl-coenzyme M reductase) are ancestral to all prokaryotes, while non-redox enzymes are derived and with multiple origins, possibly due to lateral gene transfer events or convergent evolution. I propose that the patterns observed are a product of the drastic changes during early Earth history, namely a hypothesized “nickel famine” or the Great Oxidation Event, which acted as selective pressures.

<p>      Chemical reactions in micron-sized droplets under ambient conditions are often orders of magnitude faster than the equivalent bulk reactions due to the large interfacial effects. The investigation of the underlying mechanisms driving the unique surface chemistry of droplets, as well as their applications and implications in synthesis, has garnered considerable interest. This dissertation delves into three key subtopics: (1) Exploring partial solvation as a mechanism for accelerating reactions in microdroplets, (2) Investigating the spontaneous oxidation and reduction of heteroatom double bonds induced by water radical cations and anions generated from water, and (3) Examining the role of oxazolone intermediates in prebiotic peptide synthesis and the emergence of homochirality in living systems.</p> <p>      Chemical reactions can be accelerated in microdroplets but with previously unclear mechanisms. Here we report a systematic study of organic reactions of common types in microvolumes and compare their rates with those in bulk solution. The observed interfacial area effect, molecularity effect and solvent effect provided experimental evidence for partial solvation at gas/liquid interface as one of the major contributors to the observed more than 10⁴-fold acceleration in microdroplets.</p> <p>      Recent spectroscopic results as well as computations demonstrate the existence of a strong electric field at aqueous droplet surfaces, which can result in microdroplet-specific reactions, especially their intrinsic redox properties. Spontaneous oxidation or reduction without external oxidants or reductants has been reported. One explanation for the existence of active species is dissociation of the radical cation/anion pair (H₂O^+∙/ H₂O^-∙), recently argued to occur in pure bulk water, to provide the free radical cation and radical anion. In this work, we reported spontaneous oxidation of heteroatom double bonds (e.g. sulfone to sulfonic acid, ketone to carboxylic acid) in non-aqueous microdroplets containing traces of water (<1%). Meanwhile, the simultaneous oxidation and reduction of several phosphonates was discovered, supporting the radical pair as the source of reactive species in water microdroplets.</p> <p>      One implication of microdroplet chemistry lies in its connection to prebiotic synthesis. Peptide formation from amino acids is thermodynamically unfavorable but a recent study provided evidence that the reaction occurs at the air/solution interfaces of aqueous microdroplets. Here we show that (i) the suggested amino acid complex in microdroplets undergoes dehydration to form oxazolone; (ii) addition of water to the oxazolone forms the dipeptide; and (iii) reaction of oxazolone with other amino acids forms tripeptides. Furthermore, the chirality of the reacting amino acids is preserved in the oxazolone, and strong chiral selectivity is observed when converting the oxazolone to tripeptide. This last fact ensures that optically impure amino acids will undergo chain extension to generate homochiral peptides. Peptide formation in bulk by wet-dry cycling shares a common pathway with the microdroplet reaction, both involving the oxazolone intermediate.</p>

<p>A key problem in the origin of life is to understand how an autocatalytic, self-replicating biopolymer system may have originated from a non-living chemical system. This thesis presents mathematical and computational models that address this issue. We consider a reaction system in which monomers (nucleotides) and polymers (RNAs) can be formed by chemical reactions at a slow spontaneous rate, and can also be formed at a high rate by catalysis, if polymer catalysts (ribozymes) are present. The system has two steady states: a ‘dead’ state with a low concentration of ribozymes and a ‘living’ state with a high concentration of ribozymes. Using stochastic simulations, we show that if a small number of ribozymes is formed spontaneously, this can drive the system from the dead to the living state. In the well mixed limit, this transition occurs most easily in volumes of intermediate size. In a spatially-extended two-dimensional system with finite diffusion rate, there is an optimal diffusion rate at which the transition to life is very much faster than in the well-mixed case. We therefore argue that the origin of life is a spatially localized stochastic transition. Once life has arisen in one place by a rare stochastic event, the living state spreads deterministically through the rest of the system. We show that similar autocatalytic states can be controlled by nucleotide synthases as well as by polymerase ribozymes, and that the same mechanism can also work with recombinases, if the recombination reaction is not perfectly reversible. Chirality is introduced into the polymerization model by considering simultaneous synthesis and polymerization of left- and right-handed monomers. We show that there is a racemic non-living state and two chiral living states. In this model, the origin of life and the origin of homochirality may occur simultaneously due to the same stochastic transition.</p> / Doctor of Philosophy (PhD)

This thesis explores the question of why life can not be revived when death occurs due to lack of resources. For example, why can't something as simple as E.coli be revived after its death? The hypothesis is that death is not defined by the end of metabolism itself, but rather a continued metabolism which in turn destructs the entity itself. Consequently, a virus should not be capable of ”dying” due to its lack of metabolism. To study self replication, a recent mathematical model utilising Gillespie's algorithm and differential equations has been explored. Using this model, real systems such as the Formose reaction can be modeled. Furthermore, an analytical analysis has been carried out in order to study what impact a side reaction will have on a self replicating system's total growth rate. The result of the analysis states that the growth rate of a self replicating system peaks when all the reactions have the same reaction rate, and declines as the reaction rate of a side reaction increases. In conclusion, a self replicating system that either contains a side reaction or is coupled with another self replicating system can suffer an irreversible death. The reason for this is the metabolism that occurs when the resources have been depleted. At this point, other reactions not belonging to the main metabolism can destroy the self replication. This argument strengthens the hypothesis that a virus does not die in the same way as a living cell, as it does not have a metabolism of its own.

El origen de la vida en la Tierra es una de las preguntas más difíciles presentadas a la ciencia. En los últimos 60 años, ha habido un progreso considerable en entender cómo moléculas relativamente sencillas, que son relevantes para la vida, pueden ser generadas espontáneamente o pueden llegar a la Tierra desde el espacio. Además, los análisis de la evolución de la historia de ácidos nucleicos, los cuales almacenan la información genética, apuntan a un ancestro común universal ya extinto. Los estudios del origen de la vida ofrecen muchas pistas que apuntan hacia un origen común, quizás no solo en el Tierra sino también en algún otro punto del sistema solar. Debido al largo tiempo transcurrido desde que la Tierra empezó a albergar vida, las pistas más antiguas de los primeros organismos se han perdido. Es muy poco probable encontrar exactamente cómo fue este primer organismo. Sin embargo, en los últimos años la biología sintética ha logrado progresar mucho en la modificación de biomoléculas, en particular, los ácidos nucleicos. Es posible que pronto podamos construir y comprender un sistema minimalista en el cual las moléculas puedan copiarse a sí mismas dentro de una célula rudimentaria. El estudio de un sistema así podría permitirnos develar el origen de los primeros organismos. / The origin of life on Earth is one of the most challenging questions in science. In the last 60 years, considerable progress has been made in understanding how simple molecules relevant to life can be generated spontaneously or are known to arrive to Earth from space. Additionally, analysis of the evolution history of nucleic acids, which are the repository of genetic information, points to a now extinct, universal common ancestor for all life on Earth. The studies of the origin of life offer many clues towards a common origin, perhaps not just on Earth but somewhere else in the solar system. However due to the length of time that the Earth has harbored life, the oldest clues of the first organisms are mostly gone. It is unlikely to find exactly what this first organism was like. Nevertheless, in the last few years, synthetic biology has made remarkable progress at modifying biomolecules, particularly nucleic acids. It is possible that soon we will be able to construct and understand a minimalistic system in which molecules can copy themselves in a protocell. The study of such systems could shed light into the origin of the first organisms.

I present detailed mechanistic analysis on the chemistry of glyoxylate as it pertains to forming biologically relevant molecules on the Hadean Earth. Chemistry covered includes: 1) the dimerization of glyoxylate to form dihydroxyfumarate(DHF), a heretofore unknown reaction, important to substantiating Eschenmoser's glyoxylate scenario. 2) Formation of sugars from polymerization of glyoxylate. 3) Formation of tartrate and sugar acids from high pH reactions of DHF. 4) Formation of glycine polypeptides from glyoxylate by transamination and coupling promoted by hexamethylenetetramine. 5) Formation of glyoxylate under conditions which could be plausibly found on the early earth.

Formamide is a solvent of great interest to prebiotic chemists because it is liquid over a wide range, it is less volatile than either water or HCN, and it possesses a versatile reactivity. When formamide is heated in the presence of minerals or inorganic catalysts, a variety of products including purine nucleobases are generated. Irradiation of formamide reaction solutions with ultraviolet light increases the yield and diversity of products, and eliminates the need for a mineral catalyst. We have also performed formamide reactions in the presence of pyrite, a mineral which is likely to have been available on the primordial Earth, under a variety of atmospheric conditions. Our results indicate the greatest yield and diversity of products result from the combination of a pyrite mineral catalyst, heat, UV irradiation, and a carbon dioxide atmosphere. Purine nucleobases are simple to synthesize in model reactions and they stack well in aqueous solution; it has been hypothesized that the first nucleic acids were composed of only purine bases, and that water-soluble, cationic, aromatic molecules with large stacking surfaces (“”molecular midwives””) may have aided the assembly of the earliest nucleic acid analogs. We have characterized the interactions of various intercalators with a standard DNA duplex as well as with an antiparallel homopurine DNA duplex and have determined that molecules which possess four or more rings and a curved shape interact selectively with all-purine DNA; such molecules can serve as models for putative prebiotic midwives.

Made available in DSpace on 2016-04-28T14:16:23Z (GMT). No. of bitstreams: 1 Gizele Daumichen Gasparri.pdf: 1331055 bytes, checksum: 16de5ddf8cc071c7057cee0409db15d1 (MD5) Previous issue date: 2016-02-18 / Secretaria da Educação do Estado de São Paulo / In this thesis we discuss the theory of origin of life proposed by the Soviet biochemist, Alekandr Ivanovich Oparin (1894-1980), taking into account aspects of its development and some influences uppon his ideas. In addition, we analyze how this issue is presented in teaching materials aimed at high school. To accomplish this study, we have been studing original Oparin s texts, especially his 1924 article - Origin of life and the books published in 1938 - Origin of life - and 1956 - Origin of life on the Earth both translated into English under his supervision Oparin based his theory not only in dialectical materialism, but also, in Darwinism. Thus, he was able to sustain his opposition to the theory of spontaneous generation. Another point presented in this thesis is an analysis of the teaching materials used in public schools of São Paulo, which has revealed that Oparin's theory is presented in a superficial way, reinforcing the linear view of progress and continuity in Science / Nesta dissertação apresentaremos a teoria da origem da vida proposta pelo bioquímico soviético, Alekandr Ivanovich Oparin (1894-1980), aspectos de seu desenvolvimento e algumas influências na organização de suas ideias. Além disso, analisamos como o tema é apresentado em materiais didáticos voltados ao Ensino Médio. Para realizarmos esse estudo estudamos os originais de Oparin, especialmente seu artigo de 1924 Origin of life e os livros publicados em 1938 Origin of life e 1956 Origin of life on the Earth , ambos traduzidos para o inglês sob sua supervisão. Recorremos também a traduções em espanhol e português de seus textos. Oparin fundamentou sua teoria não só no materialismo dialético, mas também, no darwinismo. Com isso, foi capaz de sustentar sua oposição à teoria da geração espontânea. Outro ponto importante discutido nesta dissertação é a análise de material didático utilizado no terceiro ano do Ensino Médio das escolas públicas do estado de São Paulo, a qual revelou que a teoria de Oparin é apresentada de forma superficial, reforçando a visão linear de progresso e continuidade da ciência

Natural gas, primarily methane (CH4), is produced in substantial amounts in ultramafic-hosted hydrothermal systems. These systems could also generate oil (heavier hydrocarbons) and the first building blocks of life (prebiotic molecules). In the presence of iron bearing minerals, serpentinisation reactions generate H2. Subsequently, CH4 could be synthesised by Fischer-Tropsch Type (FTT) reaction (4H2 + CO2 → CH4 + 2H2O) which is an abiotic process. This has lead to the idea of abiotic formation of larger organic molecules. Both thermodynamics and laboratory work support this idea, yet field data have been lacking. This study focuses on determining the organic content of fluids from ultramafic-hosted hydrothermal systems from the Mid-Atlantic Ridge (MAR) and the origin of the compounds. Fluids were collected from the Lost City, Rainbow, Ashadze and Logatchev vent fields during the EXOMAR (2005), SERPENTINE (2007), MoMARDREAMnaut (2007) and MOMAR08-Leg2 (2008) cruises conducted by IFREMER, France. A SBSE-TD-GC-MS technique was developed and used to extract, concentrate, separate and identify compounds in the fluids. Hydrothermally derived compounds appeared to consist mainly of hydrocarbons and O-bearing molecules. In addition, some amino acids were detected in the fluids by ULPC-ESI-QToF-MS but their origin will need to be determined. The organic content of the Rainbow fluids did not show intra field variability unlike differences could be noted over the years. In order to address the question of the source of the molecules, compound specific carbon isotopic analyses were carried out and completed with a bacterial (Pyrococcus abyssi) hydrothermal degradation experiment. The δ13C data fall in the range of -40 to -30‰ (vs. V-PDB), but individual δ13C values preclude the identification of a biogenic or abiogenic origin of the compounds. The degradation experiment, however, suggests an abiogenic origin of a portion of saturated hydrocarbons whereas carboxylic acids would be biogenic, and aromatic compounds would be thermogenic. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Submitted. Paper 3: Submitted. Paper 4: Submitted. / MoMARnet