Special Issue "Origin of Cellular Life"

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Chemistry".

Deadline for manuscript submissions: closed (30 March 2016)

Special Issue Editors

Guest Editor
Prof. Dr. David Deamer

Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, USA
Website | E-Mail
Phone: 831 459 5158
Interests: membrane biophysics; nanopore sequencing; origin of cellular life
Guest Editor
Dr. Bruce Damer

1. Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, USA
2. DigitalSpace Research, Boulder Creek, CA 95006, USA
Website | E-Mail
Interests: origin of life; computational modeling; space science; theoretical biology

Special Issue Information

Dear Colleagues,

Recently, we set up two Special Issues, which will incorporate related papers that reflect a sequence of events leading to the origin of life on Earth nearly four billion years ago. The present Special Issue, edited by Professor David Deamer and Dr. Bruce Damer, will focus on processes by which organic compounds and products of prebiotic polymerization reactions can undergo self-assembly into encapsulated systems. These systems are referred to as protocells, and are capable of energy-dependent polymerization processes, as well as growth of their membranous boundaries. Such systems are now at the cutting edge of current research, with a real potential to become the first form of artificial life to be demonstrated in the laboratory. Another Special Issue, “The Emergence of Life: From Chemical Origins to Synthetic Biology”, edited by Professor Pier Luigi Luisi, will be devoted to the origin of molecular order and will be organized into four different sections. For more information, please refer to https://www.mdpi.com/journal/life/special_issues/emergence_of_life.

The two Special Issues are now open for submissions. Prospective authors should first send a short abstract or tentative title to the Editorial Office. If the editors deem the topic to be appropriate for inclusion in one of the Special Issues, the author will be encouraged to submit a full manuscript.

Prof. Dr. David Deamer
Dr. Bruce Damer
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 650 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • primitive metabolism
  • prebiotic polymerization
  • encapsulation processes
  • minimal cells
  • origin of cellular life

Published Papers (10 papers)

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Research

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Open AccessArticle Flexible Proteins at the Origin of Life
Received: 13 March 2017 / Revised: 10 May 2017 / Accepted: 24 May 2017 / Published: 5 June 2017
Cited by 2 | PDF Full-text (3025 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Almost all modern proteins possess well-defined, relatively rigid scaffolds that provide structural preorganization for desired functions. Such scaffolds require the sufficient length of a polypeptide chain and extensive evolutionary optimization. How ancestral proteins attained functionality, even though they were most likely markedly smaller [...] Read more.
Almost all modern proteins possess well-defined, relatively rigid scaffolds that provide structural preorganization for desired functions. Such scaffolds require the sufficient length of a polypeptide chain and extensive evolutionary optimization. How ancestral proteins attained functionality, even though they were most likely markedly smaller than their contemporary descendants, remains a major, unresolved question in the origin of life. On the basis of evidence from experiments and computer simulations, we argue that at least some of the earliest water-soluble and membrane proteins were markedly more flexible than their modern counterparts. As an example, we consider a small, evolved in vitro ligase, based on a novel architecture that may be the archetype of primordial enzymes. The protein does not contain a hydrophobic core or conventional elements of the secondary structure characteristic of modern water-soluble proteins, but instead is built of a flexible, catalytic loop supported by a small hydrophilic core containing zinc atoms. It appears that disorder in the polypeptide chain imparts robustness to mutations in the protein core. Simple ion channels, likely the earliest membrane protein assemblies, could also be quite flexible, but still retain their functionality, again in contrast to their modern descendants. This is demonstrated in the example of antiamoebin, which can serve as a useful model of small peptides forming ancestral ion channels. Common features of the earliest, functional protein architectures discussed here include not only their flexibility, but also a low level of evolutionary optimization and heterogeneity in amino acid composition and, possibly, the type of peptide bonds in the protein backbone. Full article
(This article belongs to the Special Issue Origin of Cellular Life)
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Open AccessArticle Prebiotic Factors Influencing the Activity of a Ligase Ribozyme
Received: 31 January 2017 / Revised: 28 March 2017 / Accepted: 1 April 2017 / Published: 6 April 2017
Cited by 1 | PDF Full-text (2855 KB) | HTML Full-text | XML Full-text
Abstract
An RNA-lipid origin of life scenario provides a plausible route for compartmentalized replication of an informational polymer and subsequent division of the container. However, a full narrative to form such RNA protocells implies that catalytic RNA molecules, called ribozymes, can operate in the [...] Read more.
An RNA-lipid origin of life scenario provides a plausible route for compartmentalized replication of an informational polymer and subsequent division of the container. However, a full narrative to form such RNA protocells implies that catalytic RNA molecules, called ribozymes, can operate in the presence of self-assembled vesicles composed of prebiotically relevant constituents, such as fatty acids. Hereby, we subjected a newly engineered truncated variant of the L1 ligase ribozyme, named tL1, to various environmental conditions that may have prevailed on the early Earth with the objective to find a set of control parameters enabling both tL1-catalyzed ligation and formation of stable myristoleic acid (MA) vesicles. The separate and concurrent effects of temperature, concentrations of Mg2+, MA, polyethylene glycol and various solutes were investigated. The most favorable condition tested consists of 100 mM NaCl, 1 mM Mg2+, 5 mM MA, and 4 °C temperature, whereas the addition of Mg2+-chelating solutes, such as citrate, tRNAs, aspartic acid, and nucleoside triphosphates severely inhibits the reaction. These results further solidify the RNA-lipid world hypothesis and stress the importance of using a systems chemistry approach whereby a wide range of prebiotic factors interfacing with ribozymes are considered. Full article
(This article belongs to the Special Issue Origin of Cellular Life)
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Open AccessArticle Mobility of a Mononucleotide within a Lipid Matrix: A Neutron Scattering Study
Received: 21 October 2016 / Revised: 23 December 2016 / Accepted: 29 December 2016 / Published: 4 January 2017
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Abstract
An essential question in studies on the origins of life is how nucleic acids were first synthesized and then incorporated into compartments about 4 billion years ago. A recent discovery is that guided polymerization within organizing matrices could promote a non-enzymatic condensation reaction [...] Read more.
An essential question in studies on the origins of life is how nucleic acids were first synthesized and then incorporated into compartments about 4 billion years ago. A recent discovery is that guided polymerization within organizing matrices could promote a non-enzymatic condensation reaction allowing the formation of RNA-like polymers, followed by encapsulation in lipid membranes. Here, we used neutron scattering and deuterium labelling to investigate 5′-adenosine monophosphate (AMP) molecules captured in a multilamellar phospholipid matrix. The aim of the research was to determine and compare how mononucleotides are captured and differently organized within matrices and multilamellar phospholipid structures and to explore the role of water in organizing the system to determine at which level the system becomes sufficiently anhydrous to lock the AMP molecules into an organized structure and initiate ester bond synthesis. Elastic incoherent neutron scattering experiments were thus employed to investigate the changes of the dynamic properties of AMP induced by embedding the molecules within the lipid matrix. The influence of AMP addition to the lipid membrane organization was determined through diffraction measurement, which also helped us to define the best working Q range for dynamical data analysis with respect to specific hydration. The use of different complementary instruments allowed coverage of a wide time-scale domain, from ns to ps, of atomic mean square fluctuations, providing evidence of a well-defined dependence of the AMP dynamics on the hydration level. Full article
(This article belongs to the Special Issue Origin of Cellular Life)
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Open AccessArticle A Hypothesis: Life Initiated from Two Genes, as Deduced from the RNA World Hypothesis and the Characteristics of Life-Like Systems
Received: 7 June 2016 / Revised: 22 July 2016 / Accepted: 25 July 2016 / Published: 2 August 2016
Cited by 3 | PDF Full-text (2451 KB) | HTML Full-text | XML Full-text
Abstract
RNA played a central role in the emergence of the first life-like system on primitive Earth since RNA molecules contain both genetic information and catalytic activity. However, there are several drawbacks regarding the RNA world hypothesis. Here, I briefly discuss the feasibility of [...] Read more.
RNA played a central role in the emergence of the first life-like system on primitive Earth since RNA molecules contain both genetic information and catalytic activity. However, there are several drawbacks regarding the RNA world hypothesis. Here, I briefly discuss the feasibility of the RNA world hypothesis to deduce the RNA functions that are essential for forming a life-like system. At the same time, I have conducted a conceptual analysis of the characteristics of biosystems as a useful approach to deduce a realistic life-like system in relation to the definition of life. For instance, an RNA-based life-like system should possess enough stability to resist environmental perturbations, by developing a cell-like compartment, for instance. Here, a conceptual viewpoint is summarized to provide a realistic life-like system that is compatible with the primitive Earth environment and the capabilities of RNA molecules. According to the empirical and conceptual analysis, I propose the hypothesis that the first life-like system could have initiated from only two genes. Full article
(This article belongs to the Special Issue Origin of Cellular Life)
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Open AccessArticle The Effect of Limited Diffusion and Wet–Dry Cycling on Reversible Polymerization Reactions: Implications for Prebiotic Synthesis of Nucleic Acids
Received: 15 April 2016 / Revised: 3 June 2016 / Accepted: 6 June 2016 / Published: 8 June 2016
Cited by 6 | PDF Full-text (1452 KB) | HTML Full-text | XML Full-text
Abstract
A long-standing problem for the origins of life is that polymerization of many biopolymers, including nucleic acids and peptides, is thermodynamically unfavourable in aqueous solution. If bond making and breaking is reversible, monomers and very short oligomers predominate. Recent experiments have shown that [...] Read more.
A long-standing problem for the origins of life is that polymerization of many biopolymers, including nucleic acids and peptides, is thermodynamically unfavourable in aqueous solution. If bond making and breaking is reversible, monomers and very short oligomers predominate. Recent experiments have shown that wetting and drying cycles can overcome this problem and drive the formation of longer polymers. In the dry phase, bond formation is favourable, but diffusion is restricted, and bonds only form between monomers that are initially close together. In the wet phase, some of the bonds are hydrolyzed. However, repositioning of the molecules allows new bonds to form in the next dry phase, leading to an increase in mean polymer length. Here, we consider a simple theoretical model that explains the effect of cycling. There is an equilibrium length distribution with a high mean length that could be achieved if diffusion occurred freely in the dry phase. This equilibrium is inaccessible without diffusion. A single dry cycle without diffusion leads to mean lengths much shorter than this. Repeated cycling leads to a significant increase in polymerization relative to a single cycle. In the most favourable case, cycling leads to the same equilibrium length distribution as would be achieved if free diffusion were possible in the dry phase. These results support the RNA World scenario by explaining a potential route to synthesis of long RNAs; however, they also imply that cycling would be beneficial to the synthesis of other kinds of polymers, including peptides, where bond formation involves a condensation reaction. Full article
(This article belongs to the Special Issue Origin of Cellular Life)
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Review

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Open AccessReview Taming Prebiotic Chemistry: The Role of Heterogeneous and Interfacial Catalysis in the Emergence of a Prebiotic Catalytic/Information Polymer System
Received: 18 August 2016 / Revised: 31 October 2016 / Accepted: 1 November 2016 / Published: 4 November 2016
Cited by 2 | PDF Full-text (874 KB) | HTML Full-text | XML Full-text
Abstract
Cellular life is based on interacting polymer networks that serve as catalysts, genetic information and structural molecules. The complexity of the DNA, RNA and protein biochemistry suggests that it must have been preceded by simpler systems. The RNA world hypothesis proposes RNA as [...] Read more.
Cellular life is based on interacting polymer networks that serve as catalysts, genetic information and structural molecules. The complexity of the DNA, RNA and protein biochemistry suggests that it must have been preceded by simpler systems. The RNA world hypothesis proposes RNA as the prime candidate for such a primal system. Even though this proposition has gained currency, its investigations have highlighted several challenges with respect to bulk aqueous media: (1) the synthesis of RNA monomers is difficult; (2) efficient pathways for monomer polymerization into functional RNAs and their subsequent, sequence-specific replication remain elusive; and (3) the evolution of the RNA function towards cellular metabolism in isolation is questionable in view of the chemical mixtures expected on the early Earth. This review will address the question of the possible roles of heterogeneous media and catalysis as drivers for the emergence of RNA-based polymer networks. We will show that this approach to non-enzymatic polymerizations of RNA from monomers and RNA evolution cannot only solve some issues encountered during reactions in bulk aqueous solutions, but may also explain the co-emergence of the various polymers indispensable for life in complex mixtures and their organization into primitive networks. Full article
(This article belongs to the Special Issue Origin of Cellular Life)
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Open AccessReview A Self-Assembled Aggregate Composed of a Fatty Acid Membrane and the Building Blocks of Biological Polymers Provides a First Step in the Emergence of Protocells
Received: 30 June 2016 / Revised: 2 August 2016 / Accepted: 9 August 2016 / Published: 11 August 2016
Cited by 6 | PDF Full-text (2149 KB) | HTML Full-text | XML Full-text
Abstract
We propose that the first step in the origin of cellular life on Earth was the self-assembly of fatty acids with the building blocks of RNA and protein, resulting in a stable aggregate. This scheme provides explanations for the selection and concentration of [...] Read more.
We propose that the first step in the origin of cellular life on Earth was the self-assembly of fatty acids with the building blocks of RNA and protein, resulting in a stable aggregate. This scheme provides explanations for the selection and concentration of the prebiotic components of cells; the stabilization and growth of early membranes; the catalysis of biopolymer synthesis; and the co-localization of membranes, RNA and protein. In this article, we review the evidence and rationale for the formation of the proposed aggregate: (i) the well-established phenomenon of self-assembly of fatty acids to form vesicles; (ii) our published evidence that nucleobases and sugars bind to and stabilize such vesicles; and (iii) the reasons why amino acids likely do so as well. We then explain how the conformational constraints and altered chemical environment due to binding of the components to the membrane could facilitate the formation of nucleosides, oligonucleotides and peptides. We conclude by discussing how the resulting oligomers, even if short and random, could have increased vesicle stability and growth more than their building blocks did, and how competition among these vesicles could have led to longer polymers with complex functions. Full article
(This article belongs to the Special Issue Origin of Cellular Life)
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Open AccessReview Constructive Approaches for Understanding the Origin of Self-Replication and Evolution
Received: 3 May 2016 / Revised: 7 July 2016 / Accepted: 7 July 2016 / Published: 13 July 2016
Cited by 7 | PDF Full-text (1854 KB) | HTML Full-text | XML Full-text
Abstract
The mystery of the origin of life can be divided into two parts. The first part is the origin of biomolecules: under what physicochemical conditions did biomolecules such as amino acids, nucleotides, and their polymers arise? The second part of the mystery is [...] Read more.
The mystery of the origin of life can be divided into two parts. The first part is the origin of biomolecules: under what physicochemical conditions did biomolecules such as amino acids, nucleotides, and their polymers arise? The second part of the mystery is the origin of life-specific functions such as the replication of genetic information, the reproduction of cellular structures, metabolism, and evolution. These functions require the coordination of many different kinds of biological molecules. A direct strategy to approach the second part of the mystery is the constructive approach, in which life-specific functions are recreated in a test tube from specific biological molecules. Using this approach, we are able to employ design principles to reproduce life-specific functions, and the knowledge gained through the reproduction process provides clues as to their origins. In this mini-review, we introduce recent insights gained using this approach, and propose important future directions for advancing our understanding of the origins of life. Full article
(This article belongs to the Special Issue Origin of Cellular Life)
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Open AccessReview Prebiotic Lipidic Amphiphiles and Condensing Agents on the Early Earth
Received: 10 December 2015 / Revised: 18 January 2016 / Accepted: 15 February 2016 / Published: 28 March 2016
Cited by 5 | PDF Full-text (2846 KB) | HTML Full-text | XML Full-text
Abstract
It is still uncertain how the first minimal cellular systems evolved to the complexity required for life to begin, but it is obvious that the role of amphiphilic compounds in the origin of life is one of huge relevance. Over the last four [...] Read more.
It is still uncertain how the first minimal cellular systems evolved to the complexity required for life to begin, but it is obvious that the role of amphiphilic compounds in the origin of life is one of huge relevance. Over the last four decades a number of studies have demonstrated how amphiphilic molecules can be synthesized under plausibly prebiotic conditions. The majority of these experiments also gave evidence for the ability of so formed amphiphiles to assemble in closed membranes of vesicles that, in principle, could have compartmented first biological processes on early Earth, including the emergence of self-replicating systems. For a competitive selection of the best performing molecular replicators to become operative, some kind of bounded units capable of harboring them are indispensable. Without the competition between dynamic populations of different compartments, life itself could not be distinguished from an otherwise disparate array or network of molecular interactions. In this review, we describe experiments that demonstrate how different prebiotically-available building blocks can become precursors of phospholipids that form vesicles. We discuss the experimental conditions that resemble plausibly those of the early Earth (or elsewhere) and consider the analytical methods that were used to characterize synthetic products. Two brief sections focus on phosphorylating agents, catalysts and coupling agents with particular attention given to their geochemical context. In Section 5, we describe how condensing agents such as cyanamide and urea can promote the abiotic synthesis of phospholipids. We conclude the review by reflecting on future studies of phospholipid compartments, particularly, on evolvable chemical systems that include giant vesicles composed of different lipidic amphiphiles. Full article
(This article belongs to the Special Issue Origin of Cellular Life)
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Other

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Open AccessEssay A Field Trip to the Archaean in Search of Darwin’s Warm Little Pond
Received: 22 March 2016 / Revised: 11 May 2016 / Accepted: 20 May 2016 / Published: 25 May 2016
Cited by 9 | PDF Full-text (6415 KB) | HTML Full-text | XML Full-text
Abstract
Charles Darwin’s original intuition that life began in a “warm little pond” has for the last three decades been eclipsed by a focus on marine hydrothermal vents as a venue for abiogenesis. However, thermodynamic barriers to polymerization of key molecular building blocks and [...] Read more.
Charles Darwin’s original intuition that life began in a “warm little pond” has for the last three decades been eclipsed by a focus on marine hydrothermal vents as a venue for abiogenesis. However, thermodynamic barriers to polymerization of key molecular building blocks and the difficulty of forming stable membranous compartments in seawater suggest that Darwin’s original insight should be reconsidered. I will introduce the terrestrial origin of life hypothesis, which combines field observations and laboratory results to provide a novel and testable model in which life begins as protocells assembling in inland fresh water hydrothermal fields. Hydrothermal fields are associated with volcanic landmasses resembling Hawaii and Iceland today and could plausibly have existed on similar land masses rising out of Earth’s first oceans. I will report on a field trip to the living and ancient stromatolite fossil localities of Western Australia, which provided key insights into how life may have emerged in Archaean, fluctuating fresh water hydrothermal pools, geological evidence for which has recently been discovered. Laboratory experimentation and fieldwork are providing mounting evidence that such sites have properties that are conducive to polymerization reactions and generation of membrane-bounded protocells. I will build on the previously developed coupled phases scenario, unifying the chemical and geological frameworks and proposing that a hydrogel of stable, communally supported protocells will emerge as a candidate Woese progenote, the distant common ancestor of microbial communities so abundant in the earliest fossil record. Full article
(This article belongs to the Special Issue Origin of Cellular Life)
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