An Extended Model for the Evolution of Prebiotic Homochirality: A Bottom-Up Approach to the Origin of Life

A generalized autocatalytic model for chiral polymerization is investigated in detail. Apart from enantiomeric cross-inhibition, the model allows for the autogenic (non-catalytic) formation of left and right-handed monomers from a substrate with reaction rates epsilon L and epsilon R, respectively. The spatiotemporal evolution of the net chiral asymmetry is studied for models with several values of the maximum polymer length, N. For N = 2, we study the validity of the adiabatic approximation often cited in the literature. We show that the approximation obtains the correct equilibrium values of the net chirality, but fails to reproduce the short time behavior. We show also that the autogenic term in the full N = 2 model behaves as a control parameter in a chiral symmetry-breaking phase transition leading to full homochirality from racemic initial conditions. We study the dynamics of the N--> infinity model with symmetric (epsilon L = epsilon R) autogenic formation, showing that it only achieves homochirality for epsilon > epsilon c, where epsilon c is an N-dependent critical value. For epsilon 相似文献   

Conformationally Restricted Chiral Peptide Nucleic Acids Derived from Azetidines

Abstract

The initial experiments towards the chemical synthesis of conformationally rigid peptide nucleic acid analogues with azetidine moieties have been described.     

Steps Towards the Formation of A Protocell: The Possible Role of Short Peptides

The paper deals with molecular self-organization leading to formation of a protocell. Plausible steps towards a protocell include: polymerization of peptides and oligonucleotides on mineral surfaces; coevolution of peptides and oligonucleotides with formation of collectively autocatalytic sets; self-organization of short peptides into vesicles; entrapment of the peptide/oligonucleotide systems in mixed peptide and simple amphiphile membranes; and formation of functioning protocells with metabolism and cell division. The established propensity of short peptides to self-ordering and to formation of vesicles makes this sequence plausible. We further suggest that evolution of a protocell produced cellular ancestors of viruses as well as ancestors of cellular organisms.     

Origin of amino acid homochirality: relationship with the RNA world and origin of tRNA aminoacylation

The origin of homochirality of l-amino acids has long been a mystery. Aminoacylation of tRNA might have provided chiral selectivity, since it is the first process encountered by amino acids and RNA. An RNA minihelix (progenitor of the modern tRNA) was aminoacylated by an aminoacyl phosphate oligonucleotide that exhibited a clear preference for l- as opposed to d-amino acids. A mirror-image RNA system with l-ribose exhibited the opposite selectivity, i.e., it exhibited an apparent preference for the d-amino acid. The selectivity for l-amino acids is based on the stereochemistry of RNA. The side chain of d-amino acids is located much closer to the terminal adenosine of the minihelix, causing them collide and interfere during the amino acid-transfer step. These results suggest that the putative RNA world that preceded the protein theatre determined the homochirality of l-amino acids through tRNA aminoacylation.     

Question 4: Short Remarks About the Origin of Homochirality

These short remarks about the origin of biological homochirality are focused on the questions related to the origin and selection of homochiral polymers and the broken mirror symmetry. They are important questions, but still equally unanswered, since the answers, I believe, closely relate to the evolutionary paradigm we accept. The prebiotic evolutionary paradigm, as it seems to me, should be based on idea of "progressive evolution of structural and functional complexity," and the typical combinatorial constraints similar to the error catastrophe, which come into being due to the very complexity, must not appear here.     

Question 7: The First Units of Life Were Not Simple Cells

Five common assumptions about the first cells are challenged by the pre-biotic ecology model and are replaced by the following propositions: firstly, early cells were more complex, more varied and had a greater diversity of constituents than modern cells; secondly, the complexity of a cell is not related to the number of genes it contains, indeed, modern bacteria are as complex as eukaryotes; thirdly, the unit of early life was an ‘ecosystem’ rather than a ‘cell’; fourthly, the early cell needed no genes at all; fifthly, early life depended on non-covalent associations and on catalysts that were not confined to specific reactions. We present here the outlines of a theory that connects findings about modern bacteria with speculations about their origins. Presented at the International School of Complexity – 4th Course: Basic Questions on the Origins of Life; “Ettore Majorana” Foundation and Centre for Scientific Culture, Erice, Italy, 1–6 October 2006.     

Interaction of Keratin K1 with Nucleic Acids on the Cell Surface

The interaction of surface proteins from A431 cells and cellular extracts with nucleic acids was investigated using affinity modification with 32P-labeled reactive oligonucleotide derivatives. Proteins with molecular weights of 68, 46, 38, and 28 kD as well as several low molecular weight proteins capable of binding to nucleic acids were found on the surface of intact cells. It was demonstrated that a protein with molecular weight of 68 kD is exposed at the cell surface, since the treatment of cells with trypsin results in the cleavage of this protein. Disruption of the integrity of the cell membrane (scrapping, treatment with trypsin, or permeabilization of the cell membrane with streptolysin O or saponin) disrupts the interaction of the reactive oligonucleotides with the cell surface proteins. Affinity modification of the cytosolic and membrane-cytosolic cell fractions with labeled oligonucleotides results in the modification of a large number of proteins, where proteins with molecular weights of 68, 46, 38, and 28 kD can be found as minor components. Surface oligonucleotide-binding proteins with molecular weight of ~68 kD were isolated by affinity chromatography after the modification of intact A431 cells with a reactive oligonucleotide derivative. The isolated surface oligonucleotide-binding proteins from A431 cells were sequenced, and one of the proteins was identified as keratin K1.     

Combinatorial Chemistry of Nucleic Acids: SELEX

A method of irrational oligonucleotide design, SELEX, is considered. Individual SELEX products, aptamers, are small molecules (40–100 nt) that have a unique three-dimensional structure, which provides for their specific and high-affinity binding to targets varying from low-molecular-weight ligands to proteins. Thus, the sophisticated biosynthesis of recognizing protein elements, antibodies, can be emulated in vitro via selection and synthesis of principally new recognizing elements based on nucleic acids.     

Oligonucleotide-templated reactions based on Peptide Nucleic Acid (PNA) probes: Concept and biomedical applications

Sensing technologies based on Peptide Nucleic Acids (PNAs) and oligonucleotide-templated chemistry are perfectly suited for biomedical applications (e.g., diagnosis, prognosis and stratification of diseases) and could compete well with more traditional amplification technologies using expensive dual-labelled oligonucleotide probes. PNAs can be easily synthesised and functionalised, are more stable and are more responsive to point-mutations than their DNA counterpart. For these reasons, fluorogenic PNAs represent an interesting alternative to DNA-based molecular beacons for sensing applications in a cell-free environment, where cellular uptake is not required.     

The TNA-Family of Nucleic Acid Systems: Properties and Prospects

This report summarizes the content of the author's lecture given at the 9th ISSOL Conference on the 'Origin of Life' in Oaxaca on 2 July 2002*. The report consists of introductory remarks followed by a reproduction of the authentic sequence of slides shown during the lecture. Each slide figure is accompanied with a short commentary on the figure's content. The lecture dealt with the structure and the properties of TNA (alpha-threofuranosyl nucleic acid) and included results of some more recent chemical investigations that had been inspired by the simplicity of TNA's molecular architecture.     

Question 1: Origin of Life and the Living State

The aim of this article is to discuss four topics: First, the origin of molecular reproduction. Second, the origin of agency – the capacity of a system to act on its own behalf. Agency is a stunning feature of human and some wider range of life. Third, to discuss a still poorly articulated feature of life noticed by the philosopher Immanuel Kant over 200 years ago: A self propagating organization of process. We have no theory for this aspect of life, yet it is central to life. Fourth, I will discuss constraints, as in Schroedinger’s aperiodic crystal (Schroedinger E, What is life? The physical aspect of the living cell, 1944), as information, part of the total non-equilibrium union of matter, energy, work, work cycles, constraints, and information that appear to comprise the living state.     

Science and the Concept of Evolution: From the Big Bang to the Origin and Evolution of Life

The common thread of evolution runs through all science disciplines, and the concept of evolution enables students to better understand the nature of the universe and our origins. “Science and the Concept of Evolution” is one of two interdisciplinary science Core courses taken by Dowling College undergraduates as part of their General Education requirements. The course examines basic principles and methods of science by following the concept of evolution from the big bang to the origin and evolution of life. Case studies of leading scientists illustrate how their ideas developed and contributed to the evolution of our understanding of the world. Evidences for physical, chemical, and biological evolution are explored, and students learn to view the evolution of matter and of ideas as a natural process of change over space and time.     

应用肽核酸探针检测鼠疫耶尔森氏菌

目的:利用特异的肽核酸(PNA)探针、链霉亲和素包被的磁珠和cy5纳米颗粒,通过荧光扫描技术,建立一种特异、快速、准确地检测鼠疫耶尔森氏菌的方法。方法:针对鼠疫耶尔森氏菌pMT1质粒上的caf1基因设计并合成一对特异PNA探针,经生物素标记后,分别与链霉亲和素包被的磁珠和cy5纳米颗粒结合;将探针与待测鼠疫耶尔森氏菌的基因组DNA杂交后,利用荧光扫描技术进行检测。探讨了多个实验因素对测定的影响,并进行了特异性和灵敏度检测。结果:建立并优化了利用PNA探针检测鼠疫耶尔森氏菌的方法,得到较好的线性关系;检测的灵敏度为0.9μg/mL(待测DNA)。结论:PNA探针与靶基因的结合不易受杂交液离子强度的影响,结合后具有较高的稳定性。本研究建立的分析方法能够灵敏、特异、稳定地对鼠疫耶尔森氏菌进行定量检测,为鼠疫的监控、诊断提供了有力手段。     

绿豆子叶衰老期间核酸代谢的变化

萌发绿豆的子叶自然衰老期间,核酸含量降低,RNA降低的幅度比DNA大。电泳分析结果表明,子叶衰老期间细胞核主带DNA明显降低;而迁移慢的卫星带DNA变化不大。在RNA各组分中,18S rRNA从衰老前期就开始降低;25S rRNA和4～5S小分子RNA到衰老后期才缓慢下降。DNase和RNase活性在子叶整个衰老期间都明显升高,是导致核酸含量下降的主要原因。~3H-核苷掺入试验表明,核酸的合成速率在子叶衰老前期有所上升,到衰老后期又降低。poly(A)~ -mRNA含量在子叶开始衰老时明显上升。     

Astronomical Sources of Circularly Polarized Light and the Origin of Homochirality

Possible astronomical sources of ultraviolet circularly polarized light(UVCPL) which might be responsible for enantiomeric selection in interstellarorganic molecules are considered, Synchrotron radiation from magnetic neutronstars has been suggested as a possible source of UVCPL. However, synchrotronradiation in these situations is not predicted to be strongly circularlypolarized. Very few such sources show optical synchrotron radiation and in thefew that do circular polarization has not been observed. Magnetic white dwarfsand white dwarf binaries (Polars) can be highly circularly polarized but anyeffect on molecular clouds and star formation regions must rely on rare chance encounters. Recent observations show that substantial levels of circularpolarization are present in reflection nebulae in star formation regions. Thismechanism produces polarized light exactly when and where it is needed inregions where star formation is occurring and organic molecules are known to be present.     

Sulfur-containing Nucleic Acids: Synthesis,Chemical Reactions in Supramolecular Biopolymer Complexes,Biological Applications

The chemical behavior of sulfur-containing oligonucleotides and their reactivity in self-assembled nucleic acids (NA) and specific NA–protein complexes is considered. Reviewed are postsynthetic approaches that allow introducing sulfur-containing linkages at preselected positions of the sugar-phosphate backbone of DNA and between neighboring nucleobases, to incorporate disulfide bridges between complementary strands of double- and triple-stranded DNAs, in large catalytic RNA, etc. Special reference is given to the site-specific chemical modifications as a tool for elucidating the structure, folding, and function of biomolecules. Structure-directed chemical reactions are shown to be helpful in detecting point mutations in DNA, targeting the modifications on specific positions of NA, probing the molecular recognition in protein–DNA interfaces, studying the conformational dynamics of nucleic acids, and discriminating between different folding models.     

Origin of life: Consideration of alternatives to proteins and nucleic acids

Summary Starting with relatively simple, non-hydrolyzable compounds in aqueous solution, entirely spontaneous condensations give rise to polymers that contain purines, pyrimidines, amino acids, coenzymes, lipid components and even phosphate. The presence of certain lipid micelles allows significant product formation at millimolar substrate concentrations. The first step involves formation of a Michael adduct from--unsaturated carbonyl compounds and various nucleophiles. Polymerization of these adducts occurs via sequential Knoevenagel condensations. All reactions take place readily at temperatures below 45°. The polymers can act as macromolecular catalysts as evidenced by hydrolytic activity. The purines and pyrimidines in the polymers appear to be capable of both base pairing and stacking interactions with ribonucleic acids. Specific examples of potential alternatives to base pairing are presented. These results are discussed from the standpoint of the spontaneous development of reproducing molecules. Proteins and nucleic acids may be evolutionary developments which have displaced earlier biopolymers.     

Peptide Amyloids in the Origin of Life

How life can emerge from non-living matter is one of the fundamental mysteries of the universe. A bottom-up approach to this problem focuses on the potential chemical precursors of life, in particular the nature of the first replicative molecules. Such thinking has led to the currently most popular idea: that an RNA-like molecule played a central role as the first replicative and catalytic molecule. Here, we review an alternative hypothesis that has recently gained experimental support, focusing on the role of amyloidogenic peptides rather than nucleic acids, in what has been by some termed “the amyloid-world” hypothesis. Amyloids are well-ordered peptide aggregates that have a fibrillar morphology due to their underlying structure of a one-dimensional crystal-like array of peptides in a β-strand conformation. While they are notorious for their implication in several neurodegenerative diseases including Alzheimer's disease, amyloids also have many biological functions. In this review, we will elaborate on the following properties of amyloids in relation to their fitness as a prebiotic entity: they can be formed by very short peptides with simple amino acids sequences; as aggregates they are more chemically stable than their isolated component peptides; they can possess diverse catalytic activities; they can form spontaneously during the prebiotic condensation of amino acids; they can act as templates in their own chemical replication; they have a structurally repetitive nature that enables them to interact with other structurally repetitive biopolymers like RNA/DNA and polysaccharides, as well as with structurally repetitive surfaces like amphiphilic membranes and minerals.     

Bioorganic Chemistry and the Origin of Life

Summary A challenging theme in bioorganic chemistry is the unification of established theories of biochemistry and organic chemistry to provide new patterns for interpretation and experimentation. Especially relevant examples of such interactions can be drawn from the field of enzyme catalysis and, in particular, the role of cofactors therein.Knowledge of the chemical mechanisms by which some of the cofactors function has progressed rapidly with the aid of studies of the cofactors themselves (or compounds of related structure, models) stripped of the accompanying apoenzyme. The striking successes in this field likely arise from a fundamental resemblance between bioorganic chemistry (especially coenzyme models) and chemical evolution before the appearance of coded polypeptide enzymes.