OPEN QUESTIONS ON THE ORIGIN OF LIFE 2012
Tuesday 1 May
09:00-10:00
10:00-10:30
Registration
Opening Session
10.30-13:00
Session 1: Universality
What properties of life are universal?
THE PREMISE: At one extreme, there are researchers who contemplate life not based on carbon
(e.g. silicon) who consider solvents for life alternative to water (e.g. formamide) and entertain a
possibility of life without boundary structures (e.g. a 'living ocean' on Europa). At the other extreme,
a number of scientists claim that the severe constrains on life imposed by physics and chemistry
enforce DNA as the necessary genetic polymer and the universality of energy transduction systems
and core metabolism. The purpose of considering this question is to flesh out the scientific
arguments for and against the universality of different properties of life, and perhaps to reach a
consensus on the likely commonality between all forms of life. This question is highly topical in view
of the rapidly increasing number of recent discoveries of extra-solar planets and the quest for
finding habitable ones among them.
Is Water a Universal Solvent for Life?
Andrew Pohorille (NASA Ames Research Center)
There are strong reasons to believe that the laws, principles and constraints of
physics and chemistry are universal. It is much less clear how this universality
translates into our understanding of the origins of life. Conventionally, discussions of
this topic focus on chemistry that must be sufficiently rich to seed life. Although this
is clearly a prerequisite for the emergence of living systems, I propose to focus
instead on self-organization of matter into functional structures capable of
reproduction, evolution and responding to environmental changes. In biology, most
essential functions are largely mediated by non-covalent interactions (interactions
that do not involve making or breaking chemical bonds). Forming chemical bonds is
only a small part of what living systems do.
There are specific implications of this point of view for universality. I will concentrate
on one of these implications. Strength of non-covalent interactions must be properly
tuned. If they were too weak, the system would exhibit undesired, uncontrolled
response to natural fluctuations of physical and chemical parameters. If they were
too strong kinetics of biological processes would be slow and energetics costly. This
balance, however, is not a natural property of complex chemical systems. Instead, it
has to be achieved with the aid of an appropriate solvent for life. In particular,
potential solvents for life must be characterized by a high dielectric constant to
ensure solubility of polar species and sufficient flexibility of biological structures
stabilized by electrostatic interactions. Among these solvents, water exhibits a
remarkable trait that it also promotes solvophobic (hydrophobic) interactions
between non-polar species, typically manifested by a tendency of these species to
aggregate and minimize their contacts with the aqueous solvent. Hydrophobic
interactions are responsible, at least in part, for many self-organization phenomena
in biological systems, such as the formation of cellular boundary structures or
protein folding. Strengths of electrostatic and hydrophobic interactions are similar
and can be balanced over a wide range of temperatures, which considerably
increases the repertoire of interactions that can be used to modulate biological
functions.
Some properties of water, e.g. its chemical activity against polymerization reactions,
are considered as unfavorable to life. In actuality, this might be a favorable trait
because life requires a balance between constructive and destructive processes. For
example, molecules synthesized in response to specific conditions must be degraded
once these conditions change. Otherwise regulation of biological processes would
be virtually impossible.
Water might not be the only liquid with favorable properties for supporting life. It
has been proposed that formamide, which might be present elsewhere in the
universe in sufficient quantities to warrant interest, could be a potential alternative
to water for the origin of life. However, this will remain highly hypothetical until it is
demonstrated in further studies on its physical, chemical and biological properties it
is capable of mediating self-organization of matter and providing proper balance
between different types of non-covalent interactions.
On Universality : A few epistemology notes.
Pier Luigi Luisi
In order to make progress on the questions about the basic properties of life, is
necessary to make some epistemology remarks, which generally help to clarify basic
concepts from a systemic view. At the level of the question asked in this session, is
important to make a distinction between “essence” from the one hand, and
“properties” from the other. I say so, because I see a great confusion at this level
when people are tackling the question “what is life”-and try to possibly give a
definition. Let’s make the example of an airplane, and ask the question: “what is an
airplane?”. You cannot answer: “an airplane flies”, because this is a property. Of
course it is the most important property, but it says nothing about the essence of an
airplane. You have to answer giving the blueprint which permits the flying (motor,
wings, ratio weight/velocity...). Likewise, when you are talking about life, the
question “what is life?” cannot be answered by saying-as many do- “reproduction”.
Reproduction is a property, in each single individual can be there or not, is the most
important property when we consider a population and biodiversity- but it does not
say what the essence of life is. Here too, to touch upon the essence, you have to
provide a blueprint, the one which permits reproduction, and many other things of
the cellular life- homeostasis, metabolism, death, and so on. I believe that the best
definition of life-based on the cellular life- lies in the theory of autopoiesis, according
to which life is seen as a bounded dynamic system which is self-maintaining due to
an internal network of organization which produce the very organized system
(autopoiesis means self-production). Depending upon the inner activity, one can
have metabolic homeostasis, self-reproduction, or decay. In the time allotted, this
last point will be better illustrated.
Autonomy and universality
Leonardo Bich [1] & Luisa Damiano [2]
[1] IAS-Research Centre for Life, Mind, and Society/Department of Logic and
Philosophy of Science, University of the Basque Country, Spain.
Email: leonardo.bich@ehu.es
[2] Department of Human Sciences, University of Bergamo, Italy.
Email: luisa.damiano@unibg.it
Our answer identifies in autonomy a universal property of life, and focuses on the
issue of determining whether other biological properties related to autonomy can
be considered universal.
The contribution is structured in three steps.
The first step is dedicated to a preliminary discussion on the notion of “universality”
in biology. We draw on arguments concerning “biological universality” proposed by
different actors of the contemporary biological research (i.e. autopoietic biology,
Artificial Life, synthetic biology, and the proponents of the mechanistic or
operational explanations in biology) to support the thesis that universal properties
of life do not lie in the properties of its physico-chemical components, but in those
of the functional organization which correlates a multiplicity of elemental
components in the relational and dynamical units given by living systems.
Accordingly, we argue that a “universal biology”, conceived as the science studying
the fundamental principles of life “as it is” and “as it could be”, has to explore,
instead of the components of life, the integrated set of mechanisms which in living
systems generates the fundamental biological phenomenology.
The second step identifies the fundamental phenomenology of life in the minimal
individual biological phenomenology, which constitutes the specific biological
domain of our search for the universal properties of life.
The third steps deals with the issue of establishing whether the properties usually
used to characterize individual living systems can be considered universal properties
of life. In particular, on the basis of current relevant research within biology,
philosophy of biology and synthetic biology, we will: (a) support the thesis of the
universality of autonomy, conceived as the property of self-production emerging
from the biological individual organization; (b) discuss the universality of the
reticular and hierarchical characters of this organization; and (c) evaluate the
possibility of considering as universal properties of life other properties usually
ascribed to the autonomous organization of living systems and observed in its
terrestrial instances, such as:
1) The capability of self-distinction from the environment, with a focus on
different possible forms of compartmentalization (e.g., boundary,
cohesion...);
2) The capability of adaptive/evolutionary interaction with the environment;
3) The capability of population interaction and participation in inter-individual
communities.
13:00-14:00
Lunch
14:00-16:30
Session 2: Evidence
What would convince us that we have answered the question “How did life begin?”
THE PREMISE: The transition from non-living to living systems involves, as a key step, the formation
of a self-bounded physical system that contains interacting molecules. In many proposed scenarios,
the complexity of such an event is often underestimated, and it is typically taken for granted,
starting from the separated components. However, compared to the large amount of work done for
understanding the emergence and the evolution of functional molecules and networks (ribozymes,
catalytic peptides, simple metabolic cycles, self-replicating molecules, hypercycles and autocatalytic
sets, etc.), much less has been done for understanding the physical mechanisms underlying the
assembly of primitive cell-like structures. In particular, little attention has been given to go beyond
the general and simplistic sentence '... and later became encapsulated in a membrane-based
compartment’.
On Evidence
Pier luigi Luisi
The bottle neck of the macromolecular synthesis.
The field of the origin of life involves many centres all around the world, with a large
variety of skills and facilities. And yet, there are certain areas of great importance
that are barely touched by our investigation-and one may wonder why. One of these
is the prebiotic synthesis of macromolecules-proteins or nucleic acids. By this I do
not mean a simple polymerization of one given monomer into a homo-polymer, or
the mixture of two or more monomers into a random copolymer. I mean the
synthesis of a polypeptide with an ordered sequence in many identical copies. This
would be simply the way to arrive at the prebiotic synthesis of enzymes and/or
nucleic acids. And you may look into the literature, looking for the evidence of the
synthesis of, say, a 30-peptide in a precise primary structure, and find nothing. The
same for nucleic acid. The emphasis on “many identical copies” is particular
important, and generally neglected, particularly by the adherents to the prebiotic
RNA world. Even assuming that by random polymerization of mono-nucleotides you
make one single molecule of a self-replicating RNA- nothing will be achieved. In
chemistry, you do nothing with one single molecule. To have self-replication of A,
you need at least a dimer A.A, and then this must be present in a concentration
which defies diffusion forces. This means a concentration of ca. nano-molar, which
means that even in a microlitre you have to have many many thousand of identical
copies of A.
Thus, for me a good evidence of a big jump ahead in the field, will be the evidence
for the prebiotic synthesis of polypeptides and/or nucleic acids with an ordered
primary structure in a sizable concentration of many identical copies.
The ‘super-encapsulation’ of solutes inside lipid vesicles: a new vista for the origin
of metabolism
Pasquale Stano and Pier Luigi Luisi (Biology Dept., University of Roma Tre, Rome,
Italy. stano@uniroma3.it; luisi@mat.ethz.ch)
One of the open issues for understanding how primitive cells emerged from
separated, inanimate molecules concerns the need to encapsulate several
molecules, possibly in high local concentration, inside lipid vesicles. This is important
in order to establish mutual molecular interaction, ultimately leading to primitive
forms of metabolism.
In literature, the description of primitive cells formation from a solution containing
the molecules of interest is often just qualitative, and it is taken for granted that
such cells would co-entrap a very high number of different molecules and at the
right concentration. The limits imposed by the co-entrapment statistics and
characteristic features of stochastic phenomena are not considered. In particular, it
has not been discussed in explicit way how several different molecules could be
entrapped in the same lipid compartment and at which local concentrations.
In contrast with these expectations, recent experimental results show that lipid
vesicles are indeed able to encapsulate a very high number of molecules [1-3], even
starting from diluted solutions. Some vesicles contained solutes in the ‘crowding’
concentration regime. These evidences are especially relevant when it is considered
that the reactivity of diluted mixture is rather sluggish, whereas a spontaneous
concentration of its components could ‘switch-on’ reactions that would not occur
otherwise.
In this contribution we would like to discuss in general the problem of solute
concentration for the origin of cellular metabolism, and how to overcome it thanks
to unexpected patterns derived from the interplay between the lipid vesicle
formation and the solute encapsulation mechanisms.
[1]Souza, T.; Stano, P.; Luisi, P. L. The minimal size of liposome-based model
cells brings about a remarkably enhanced entrapment and protein synthesis.
ChemBioChem 2009, 10, 1056-1063.
[2]Luisi, P. L.; Allegretti, M.; Souza, T.; Steineger, F.; Fahr, A.; Stano, P.
Spontaneous protein crowding in liposomes: A new vista for the origin of
cellular metabolism. ChemBioChem 2010, 11, 1989-1992.
[3]Souza, T.; Steiniger, F.; Stano, P.; Fahr, A., Luisi, P. L. Spontaneous crowding
of ribosomes and proteins inside vesicles: A possible mechanism for the
origin of cell metabolism. ChemBioChem 2011, 12, 2325-2330.
Wednesday 2 May
09.30-12:30
Session 3: Emergence
How does biology emerge from chemistry?
THE PREMISE: The transformation of inanimate matter to complex life is traditionally divided into
two stages. The first, abiogenesis, involves the conversion of non-living material to simplest life, and
the second, the biological phase, is the stage on which Darwinian evolution began to operate. A key
issue with regard the problem of the origin of life is to shed light on the physicochemical relationship
between these two stages. Processes are normally characterized by driving forces and mechanisms
so the question of the origin of life will be greatly clarified if both abiogenesis and biological
evolution can be characterized in this way
How does biology emerge from chemistry?
Addy Pross
While Darwinian theory did reveal the general principles governing biological
evolution, the relevance of that landmark theory to the emergence of life from
inanimate matter (abiogenesis) remains unclear. One hundred and thirty years ago
Charles Darwin wrote in an 1882 letter to George Wallich: “I believe that I have
somewhere said….that theprinciple of continuity renders it probable that the
principle of life will hereafter be shown to be part, or consequence, of some general
law”. In this talk I will attempt to demonstrate, just as Darwin’s luminary comment
foreshadowed, that the seemingly separate processes of abiogenesis and biological
evolution are one single continuous physicochemical process. Our analysis is based
on recent developments in systems chemistry and the newly proposed concept of
dynamic kinetic stability.[1] Though the proposed unification does not offer direct
insight into the historical process of life’s emergence, it does place that remarkable
transformation within a general physicochemical framework, thereby offering new
insights into a range of biological questions, including the one of interest to this
workshop, how did life emerge from inanimate matter?
Reference
[1] A. Pross, Toward a general theory of evolution: Extending Darwinian theory
to inanimate matter, J. Syst. Chem. 2, 1, 2011.
Processes that Drove the Transition from Chemistry to Biology: Concepts and
Evidence
Andrew Pohorille (NASA Ames Research Center)
Two properties are particularly germane to the transition from chemistry to biology.
One is the emergence of complex molecules (polymers) capable of performing nontrivial functions, such as catalysis, energy transduction or transport across cell walls.
The other is the ability of several functions to work in concert to provide
reproductive advantage to systems hosting these functions. Biological systems
exhibit these properties at remarkable levels of efficiency and accuracy in a way that
appears effortless. However, dissection of these properties reveals great
complexities that are involved. This opens a question: how a simple, ancestral
system could have acquired the required properties? Other questions follow. What
are the chances that a functional polymer emerges at random? What is the
minimum structural complexity of a polymer to carry out a function at a reasonable
level of efficiency? Can we identify concrete, protobiologically plausible mechanisms
that yield advantageous coupling between different functions? These and similar
questions are at the core of the main topic of this session: how soulless chemistry
became life?
Clearly, we do not have complete answers to any of these questions. However, in
recent years a number of new and sometimes unexpected clues have been brought
to light. Of particular interest are proteins because they are the main functional
polymers in contemporary cells. The emergence of protein functions is a puzzle. It is
widely accepted that a well-defined, compact structure (fold) is a prerequisite for
function. It is equally widely accepted that compact folds are rare among random
amino acid polymers. Then, how did protein functionality start? According to one
hypothesis well folded were preceded by their poorly folded, yet still functional
ancestors. Only recently, however, experimental evidence supporting this
hypothesis has been presented. In particular, a small enzyme capable of ligating two
RNA fragments with the rate of 106 above background was evolved in vitro. This
enzyme does not look like any contemporary protein. It is very flexible and its
structure is kept together just by a single salt bridge between a charged residue and
a coordinating zinc. A similar picture emerges from studies of simple
transmembrane channels that mimic those in ancestral cells. Again, they are
extremely flexible and do not form a conventional pore. Yet, they efficiently mediate
ion transport. Studies on simple proteins that are on-going in several laboratories
hold promise of revealing crucial links between chemical and biological catalysis and
other ubiquitous cell functions.
Interaction between composition, growth and division of protobiologically relevant
vesicles and metabolic reactions that they encapsulate is an example of coupling
between simple functions that promotes reproduction and evolution. Recent studies
have demonstrated possible mechanisms by which vesicles might have evolved their
composition from fatty acids to phospholipids, thus facilitating a number of new
cellular functions. Conversely, it has been also demonstrated that an encapsulated
metabolism might drive vesicle division. These are, again, examples of processes
that might have driven the transition from chemistry to biology.
How does biology emerge from chemistry?
Rafal Wieczorek (University of Southern Denmark)
On Prebiotic Ecology, Supramolecular Selection and Autopoiesis
Proper theory for the origins-of-life should propose a logical chain of events that
would start with prebiotic soup and end with a living organism. RNA-world seems to
be the only theory for the origin-of-life that succeeds at this task. Despite heavy
criticism directed at it no alternative theories of similar scope have been put
forward.
This talk will be an attempt at providing an alternative theory for the origin-of-life
based on the so called “compartmentalistic school” approach.
We will start by the premise of prebiotic-ecology, in which complex molecules of
prebiotic soup interact with each other giving rise to supramolecular-selection, a
process in which different macromolecular assemblies are preferentially formed
basing on their contingent properties. The second premise will be a spontaneous
appearance of autopoietic entities trough the actions of supramolecular selection. It
will be argued that an emergence of hereditary evolution leading to life will
conclude such a scenario.
Finally, this consideration will result in the proposition of new set of research
directions that should be pursued by the origin-of-life scientists.
Pre-darwinian uv selection at anoxic geothermal fields: how does biology emerge
from chemistry?
Armen Y. Mulkidjanian (School of Physics, University of Osnabrück, D-49069
Osnabrück, Germany, and A.N. Belozersky Institute of Physico-Chemical Biology,
Moscow State University, Moscow 119992, Russia. amulkid@uos.de)
We believe that the virtually unlimited number of tentative scenarios of the origin of
life can be dramatically reduced by the simultaneous consideration of a variety of
external constraints [1]. These constraints can be articulated as questions, some of
which are addressed below.
A tentative answer to this question could be obtained by searching for common
chemical properties of key constituents of life. An apparent common property of
natural nucleotides is their exceptional photostability, which implies that they could
have been selected from a plethora of diverse abiotically (photo)synthesized organic
compounds under solar UV radiation [2]. Analogously, photoselection might have
facilitated the transition from complex mixtures of small organic molecules to the
“RNA world” by favoring photostable RNA-like polymers with excitonically coupled,
stacked nucleotides forming Watson-Crick pairs [2]. In addition, solar UV radiation
could support primeval syntheses not only by catalyzing photo-polymerization but
also by breaking the less photostable organic molecules and thus supplying building
blocks for new synthetic cycles [3].
Emergence vs. Evolution of life
Leonardo Bich [1] & Luisa Damiano [2]
[1]IAS-Research Centre for Life, Mind, and Society/Department of Logic and
Philosophy of Science, University of the Basque Country, Spain.
Email: leonardo.bich@ehu.es
[2] Department of Human Sciences, University of Bergamo, Italy.
Email: luisa.damiano@unibg.it
In our talk we will advocate the view according to which from the theoretical point
of view - at the current state of knowledge about minimal living systems abiogenesis and biological evolution are to be considered as two discontinuous steps
of the more comprehensive process of natural history. The main issue is to establish
how deep this discontinuity has to be considered, and what are its consequences for
the scientific investigation and explanation in this domain.
We will address the question by firstly discussing the implications and, especially,
the difficulties in applying the notion of emergence in the domain of the origins of
life. In fact, emergence is a concept mainly used in constitutive whole-parts
explanations rather than in etiological ones – the latter concerning the history of a
process leading to the occurrence of a phenomenon. What is lacking is a proper
theory of emergent processes developed enough to be implemented in the study of
the origins of life. Yet, constitutive explanations can still provide useful theoretical
tools in terms of requirements for steps towards life, thus allowing us to analyze the
relation between the emergence of life, and evolution.
Our thesis is that there are distinct mechanisms and driving forces at work
respectively in the prebiotic and biological domains, as well as different forms of
selection, and that even being alive as such is not a necessary and sufficient
condition for evolution. By taking into consideration a specific model of basic living
systems, the one based on the idea of “biological autonomy”, we will clarify and
discuss the main conceptual nodes concerning the relation between abiogenesis,
emergence and biological evolution. In the first place we will analyze in mechanistic
terms the factors that make a living system an emergent processual unit –a selfproducing and self-maintaining system- different from a chemical one, namely:
coordination, regulation and integration, contrasted with the structural stability of
physicochemical systems. On this basis, and in order to address the issue of
requirements for evolution, we will provide a further distinction between
physicochemical and living systems with respect to the modalities of interaction with
the environment.
We will conclude by arguing that an analysis of these theoretical nodes supports an
approach that goes more in the direction of a multi-step perspective on the relation
between abiogenesis and evolution, rather than of a unified one. Even though a
discontinuist framework like this seems to violate the so called “the principle of
continuity”, nonetheless it does not imply neglecting or drastically limiting the
possibility for scientific investigation in this domain. On the contrary, it requires the
development and implementation of a specific heuristics in which, as we will
maintain, the synthetic biology approach plays a fundamental role.
Metabolism and motility in prebiotic structures
Martin M. Hanczyc (Center for Fundamental Living Technology (FLinT), Institute of
Physics and Chemistry, University of Southern Denmark Campusvej 55, 5230 Odense
M Denmark, Tel: +45 6550 4438; E-mail: martin@ifk.sdu.dk)
At the very early origin of life when matter is organizing or becoming organized, selfassembly of molecular aggregates is only one step towards life. What could the next
step look like? Easily accessible, primitive chemical structures produced by selfassembly of hydrophobic substances into oil droplets may result in self-moving
agents able to sense their environment and move to avoid equilibrium. These
structures would constitute very primitive examples of life on Earth, even more
primitive than simple bilayer vesicle structures. A few examples of simple chemical
systems are presented that self-organize to produce oil droplets capable of
movement, environment remodeling, and primitive chemotaxis. These chemical
agents are powered by an internal chemical reaction based on the hydrolysis of an
oleic anhydride precursor or on the hydrolysis of HCN polymer, a plausible prebiotic
chemistry. Results are presented on both the behavior of such droplets and the
surface-active properties of HCN polymer products. Such motile agents would be
capable of finding resources while escaping equilibrium and sustaining themselves
through an internal metabolism, thus providing a working chemical model for a
possible origin of life.
The Origin of Life is a Spatially Localized Stochastic Transition
Meng Wu and Paul G Higgs (Origins Institute and Dept. of Physics and Astronomy,
McMaster University, Hamilton, Ontario L8S 4M1, Canada. higgsp@mcmaster.ca)
The creation of an autocatalytic reaction system controlled by polymers such as RNA
is the key step in the origin of life. We have previously studied scenarios for the
origin of the RNA World using mathematical models of RNA polymerization. These
models have two stationary states. In the non-living state, polymerization is possible
to some degree at a slow spontaneous rate, but the system is dominated by
monomers and short oligomers. In the living state, reaction rates are controlled by
ribozymes and there is a significant concentration of long polymers. In a large, wellmixed system, the non-living state is dynamically stable indefinitely. However, in a
finite sized region, with finite numbers of molecules, concentration fluctuations can
cause a stochastic transition from the non-living to the living state. Here, we
consider a simplified generic model of replicators that has the same essential
features as our RNA polymerization models. This allows us to investigate the effect
of the spatial distribution of replicators on the stochastic transition that leads to the
origin of life.
We consider a system of replicators on a lattice. Replicators can appear at a slow
rate by random polymerization. Replicators may also act as polymerases that
catalyze the replication of another replicator when there are two replicators on a
site. Replicators also hop to neighbouring sites at a rate h. When h is large, the
system is well-mixed, and the system tends to a low-density non-living state that is
dynamically stable. When h is small, the density converges initially to the low density
state, but a stochastic transition then occurs, leading to a high density in a localized
region. The high density patch then spreads deterministically across the lattice until
the whole system is in the living state.
The time required for the origin of life depends on the lattice size and on the
diffusion rate h. In the well-mixed limit, the transition requires global-scale
concentration fluctuations and becomes increasingly more difficult as the lattice size
increases. In the low-h case, widely-separated regions behave independently; hence
the time required decreases with lattice size. This model illustrates that life arises by
a rare stochastic event that occurs due to spatially localized concentration
fluctuations. Once the living state is established locally, it can spread
deterministically through the rest of the system. These are generic features also
possessed by more complex models with a greater degree of chemical realism.
12:30-14:00
Lunch
14:00-16:30
Session 4: Evolution
Is prebiotic evolution Darwinian?
THE PREMISE: There is no doubt that present-day life is highly open-ended. For example, a small
bacterium with genome size of about 500,000 bases has essentially infinite number of possible
states. This allowed for life to evolve finding solutions to a variety of problems, giving rise to the high
diversity of present-day life, e.g. the number of viable strains, subspecies and individual variants of
the aforementioned bacterium. In contrast, closed systems, exhibiting only relatively few possible
states, have a much more limited capacity to undergo evolution. What is the relationship between
the openness of a system and its evolvability? Is there an optimal 'openness' in this respect, and how
could one effectively utilize this insight in computational and experimental models?
Title to be confirmed
Omer Markovitch and Doron Lancet
Is there an optimal level of open-endedness that facilitates evolution, and is this
level at present-day life different then at the origin of life?
Cellular life could have emerged from properties of vesicles
Saša Svetina (Institute of Biophysics, Faculty of Medicine, University of Ljubljana and
Jožef Stefan Institute, Ljubljana, Slovenia)
The core features of the life process are growth, self-replication and evolution.
There is a general quest to reveal which properties of molecules or their
supramolecular structures enabled these phenomena to occur. This contribution
deals with the hypothesis that the emergence of cellular life could have been based
on properties of vesicles. Vesicles were instrumental for the transition from the
inanimate to living matter at least by supplying the necessary compartmentalization.
That their role could have been more essential is indicated by their spontaneous
formation and by their ability to grow, self-reproduce, and consequently evolve. The
most relevant vesicle property in this respect seems to be their shape behavior.
Vesicle shape behavior is an emergent property of membranous systems which does
not depend essentially on the sort of membrane constituents. Here we shall first
give an insight into vesicle shapes by emphasizing their generality and universality.
In continuation it will be implied that the vesicular basis of the emergence of cellular
life challenges some established and suggests some new paradigms: In its most
primitive form the life process could have proceeded through processes that took
part on the outer surface of the vesicle membrane. Membrane budding observed in
simple vesicles and in cells can be considered to be of the same physical origin, only
that the corresponding processes in cells have had acquired a high level of control.
The process of vesicle self-reproduction evolved into the present complex cell cycle
in a single route. The pivotal feature of the cell cycle is the division process, by the
replication of nucleic acids being one of the evolutionary improvements. Proteins
and nucleic acids need not to be considered as the essential elements of the life
process.
Thursday 3 May
09:30-12:30
Session 5: Reproduction and metabolism
How did metabolism and genetic replication get married?
Did metabolism and genetic replication get married on the scales of equilibria?
Vic Norris (Theoretical Biology Unit, EA 3829, University of Rouen, 76821, Mont Saint
Aignan, France)
Living systems are often forced to make a choice: either to interact, take risks and
grow or to shut themselves away, hunker down and survive. Living systems are also
highly structured. Indeed, in our "ecosystems-first", origins-of-life scenario, the most
fundamental of living systems, cells, were highly structured right from the start [1,
2]. We have argued that this structuring takes the form of extensive macromolecular
assemblies, the descendants of composomes [3], termed hyperstructures. Evidence
for hyperstructures in both eukaryotes [4] and prokaryotes [5-8] is steadily
accumulating. In bacteria, hyperstructures can be partly described by their position
on an equilibrium–non-equilibrium axis [5]. Equilibrium (or more exactly, quasiequilibrium) hyperstructures, which remain stable despite interruptions in the flow
of energy or nutrients, allow cells to survive starvation and stresses whilst nonequilibrium hyperstructures, which fall apart as a result of such interruptions, allow
growth. The existence of these types of hyperstructures helps, in part, explain how
cells overcome one of the major constraints on their evolution, namely that they
must be able to both grow in heaven and survive in hell. The explanation is that a
bacterial population comprises cells with different combinations of non-equilibrium
and equilibrium hyperstructures which give rise to a range of phenotypes [9]. This
gives rise to another question – how do cells balance these types of
hyperstructures? Put differently, and independently of levels of organisation, this
question boils down to 'How do living systems exist on the scales of equilibria?'.
At the level of cells, a possible answer to this question involves the cell cycle itself as
outlined in the Dualism hypothesis [9] where the emphasis placed on structures with
confined reactions and different dynamics may be related to the results of
simulations [10]. If the 'scales of equilibria' approach is really fundamental, it should
offer a unifying framework for coupling metabolism to the cell cycle in organisms as
different as Homo sapiens and Escherichia coli – and perhaps further still – from E.c.
to E.T. We propose that the decision to replicate involves both the intensity sensing
of non-equilibrium hyperstructures responsible for growth (via metabolism) and the
quantity sensing of equilibrium hyperstructures responsible for survival. In reexamining one of the best understood of all systems, the initiation of chromosome
replication in E. coli, we find some evidence that, even after billions of years of
evolution, the fundamentals of life on the scales may still be operating [11].
References
[1] A. Hunding et al., Bioessays 28, 399 (2006).
[2] V. Norris, and A. Delaune, Origins of Life and Evolution of Biospheres 40, 365
(2010).
[3] D. Segre, D. Ben-Eli, and D. Lancet, Proc Natl Acad Sci U S A 97, 4112 (2000).
[4] R. Narayanaswamy et al., Proc Natl Acad Sci U S A 106, 10147 (2009).
[5] V. Norris et al., Annual review of microbiology 61, 309 (2007).
[6] P. M. Llopis et al., Nature 466, 77 (2010).
[7] K. Nevo-Dinur et al., Science (New York, N.Y 331, 1081 (2011).
[8] W. Wang et al., Science (New York, N.Y 333, 1445 (2011).
[9] V. Norris, Medical hypotheses 76, 706 (2011).
[10] A. Kamimura, and K. Kaneko, Phys. Rev. Lett. 105, 268103 (2010).
[11] V. Norris, and P. Amar, in Modelling complex biological systems in the
context of genomics, edited by P. Amar et al. (EDF Sciences, Evry, France,
2012), p. in press.
2.00 pm Session 6 Chemistry
Do We Understand Enough About Prebiotic Chemistry to Formulate Meaningful Hypotheses About
the Origin of Life?
THE PREMISE: Since Miller's 1953 demonstration of the synthesis of amino acids from reduced
gases using an electric discharge, there has been a continual focus in origins of life research to find
novel 'prebiotic' ways of making the molecules of modern biochemistry, including lipids, amino
acids, nucleotides and their polymers. Despite almost 60 years of research, many obstacles remain.
One possible reason is that the first replicating systems did not use similar compounds in their
biochemistry. Indeed, amino acids are actually a rather small percentage of the total number of
compounds formed in an electric discharge; more than 95 per cent of the products of such
experiments remain unidentified. In carbonaceous chondrites, which are often presented as
evidence that the 'molecules of life' are ubiquitous in the cosmos, compounds found in modern
biochemistry again make up a vanishingly small fraction (<<1%) of the total small molecule organic
inventory. Given that we know so little about the available compound types, is a direct
reconstruction of a modern cell from such components the best way, or even a reasonable way to
approach the problem of the origin of life? If not, what would we like or need to know to be able to
approach this problem more productively?
Search for the most primitive membranes: some remaining problems
Yoichi Nakatani (University of Strasbourg)
A cell enclosed by a membrane is the common unit structure shared by all living
oganisms. The understanding of origin of membranes is therefore central to an
understanding of the origin of life. Terpenoids are membrane constituents in
Archaea and are essential to reinforce the membranes in Eucarya (sterols) and
Procarya hopanoids). We proposed a phylogenetic tree of membrane terpenoids,
and from a retrograde analysis, we postulated that single-chain polyprenyl
phosphates might be a candidate of the most primitive membrane constituents (1).
We have synthesized phosphates of single polypropenyl chain, and demonstrated
that these lipids do form spontaneously vesicles in water in a wide pH range, when
the chain contains 15 to 30 C-atoms (2, 3). We showed then that a clay,
montmorillonite K-10 mediates the condensation of isopentenol (C5) with prenol
(C5) to generate a mixture of isomeric C10 prenols (4), supporting the hypothesis
that polyprenols may have been formed in prebiotic conditions and possibly
constitute primitive membranes (5). These steps have been repeated, and led from
C10 to C15 prenols.
We will discuss about some remaining problems (6):
1. The origin of the C5 units and the local concentration. What might be the
starting materials of the C5 units, and how and where could the C5 units be
obtained in prebiotic conditions ? It is also clear that a minimal
concentration (cmc) must be attained locally before any self-organization of
lipids to vesicles in water.
2. The prevalence of phosphates and the phosphorylation of alcohol.
Phosphates are present in all head-groups of membrane lipids and the
indispensable role of phosphates in many aspects of biochemistry is assigned
to the specific properties of this group (7). But, this ubiquitous role of
phosphates is in sharp contrast with the low abundance of phosphorus in
the Earth crust (0.12 %). Furthermore, the phosphorylation of an alcohol is a
difficult task. How could polyprenols be phosphorylated and how did
polyprenyl phosphates reach a minimal concentration to form vesicles in
water?
References
[1] Ourisson, G., Nakatani, Y. (1994) "The terpenoid theory of the origin of
cellular life : the evolution of terpenoids to cholesterol, Chemistry & Biology,
11-23.
[2] Pozzi, G., Birault, V., Werner, B., Dannenmuller, O., Nakatani, Y., Ourisson,
G., Terakawa, S. (1996). Single-chain polyterpenyl phosphates form primitive
membranes, Angew. Chem. Int. Ed. Engl., 35, 177-180.
[3] Streiff, S., Ribeiro, N., Wu, Z., Gumienna-Kontecka, E., Elhabiri, M., AlbrechtGary, A. M., Ourisson., G., Nakatani, Y. (2007), "Primitive" membrane from
polyprenyl phosphates and polyprenyl alcohols, Chemistry and Biology, 14,
313-319.
[4] Désaubry, L., Nakatani, Y., Ourisson, G. (2003). Toward higher polyprenols
under ‘prebiotic’ conditions, Tetrahedron Lett., 44, 6959-6961.
[5] Ourisson, G., Nakatani, Y. (1999) Origins of cellular life: molecular
foundations and new approaches, Tetrahedron, 55, 3283-3190.
[6] Ourisson, G., Nakatani, Y. (2006) A Rational Approach to the Origin of Life:
From Amphilic Molecules to Protocells. Some Plausible Solutions, and Some
Real Problems, In: Lectures in Astrobiology, M., Gargaud, B., Barbier, H.,
Martin, J., Reisse, (Eds), Vol. 1: Part 2, 29-48, Springer-Verlag, ISBN 978-3540-29004-9, Berlin, Heidelberg.
[7] Westheimer, F., H., (1987) Why Nature chose phosphates?. Science, 235,
1173-1178.
Ionizing radiation: Friend or foe of the origins of life?
Z. P. Zagórski and E.M. Kornacka (Centre for Radiation Research, Institute of Nuclear
Chemistry and Technology, PL-03-195 Warsaw, Poland)
The Early Earth was from the beginnings penetrated by ionizing radiation, of
intensity much higher than now. The origins of radiations were very different, from
sources present on Earth, like radiations of radioactive elements, to radiations
coming from the outer space like cosmic radiation. Therefore all kinds ionizing
radiations were represented, of different particles and quanta and of very different
quality radiations expressed by their LET value (linear energy transfer) [1]. The
action of radiation can be direct on molecules absorbing it, or indirect one, by
products of radiolysis of the medium on dispersed admixtures. Even high LET value
radiations of low penetration, like alphas from radon, abundant on early Earth, were
of enormous influence, because they were able to penetrate everything exposed to
the air, including first living creatures exchanging the air [2]. Whatever the detailed
chemical effects, investigated and generalized by the radiation chemistry,
absorption of ionizing radiation means a supply of energy to the system,
participating in the so called “chemical evolution” (no direct analogy to the
Darwinian evolution). Chemical changes induced in the media by radiation were of
prebiotic character but could not alone be responsible for decisive (as far we know)
character for the formation of life. For instance they could not contribute to the
separation of racemic mixtures into separate enantiomorphic species. Answering the
question in the title of the summary, one can say that the ionizing radiation could be
a “friend” as being involved in creation of organics (e.g of methane from carbon
dioxide [3], or polymerization of acetylene, probably present in aqueous systems
near volcanos). As concerns radiation being a “foe”, one can consider
depolimerization action on compounds already formed before. On the other hand,
the chemical bonds disruptive action on information transmitting compounds (RNA
and later DNA) was contributing to mutations, decisive elements in Darwinian
evolution of Life. In conclusion, the role of ionizing radiation in origins of life and
early evolution cannot be neglected and demands further research.
References:
[1] Z.P. Zagórski, Role of radiation chemistry in the origin of life, early evolution
and in transportation through cosmic space. Chapter 5 in “Astrobiology:
Emergence, Search and Detection of Life” (V.A. Basiuk Ed.), American
Scientific Publishers, 2010, pp 97 – 154.
[2] Z.P. Zagórski, Possible role of radon in prebiotic chemistry and in early
evolution of Life on Earth. Nukleonika 55, 555-558 (2010).
[3] Z.P. Zagórski, E.K.Kornacka, W. Głuszewski, in preparation
Friday 4 May
09:30-12:00
Session 7: Where?
Where did life begin?
THE PREMISE: Evolution described by the Darwinian theory may be depicted as a phylogenetic tree
and a postulated root representing the last common ancestor and its precursors. It is sometimes
believed that solving the question of the Origins of Life will need to bring information about the
lapse of time separating the Origin from the last common ancestor in the postulated root. Scenarios
have been proposed based on possible environments assumed on the early Earth (Ocean, vents...).
Alternatively, physicochemical principles can be used to reach conclusion about how selforganisation proceeds and chemistry can be helpful in bringing to light the related processes.
Where did life begin?
Robert Pascal (Institut des Biomolécules Max Mousseron, CNRS - University of Montpellier
1& Montpellier 2, Montpellier, France)
Following J. Monod (1970) life had almost no chance to emerge so that the
questions about its origins should remain out of the field of science. But this option
that leaves an essential question out of the reach of science is not acceptable a
priori. Scientific investigations in this field should on the contrary be aimed at
determining conditions under which the probability is different from zero, which
could be of some help in identifying possible environments for the origins of life.
This question may be treated from a detailed analysis of possible chemical pathways
but information can also be obtained from physicochemical principles governing
self-organization (Pascal & Boiteau, 2011). The necessity for living systems and other
self-organizing systems to operate in an irreversible way and for any chemical
intermediates with a significant lifetime to be protected from a direct evolution
toward equilibrium (Eschenmoser, 1994) will be shown to raise quantitative
thermodynamic constraints on the availability of free energy sources. Using this
information, a nonzero probability for the emergence of life can be predicted in
environments where the corresponding free energy potential is available, namely
environments in which photochemical processes are possible or that can be reached
by powerful activating agents formed in the atmosphere by lightning, impacts or
photochemistry.
References
Monod J (1970) Le hasard et la nécessité. Odile Jacob, Paris
Pascal R, Boiteau L (2011) Energy flows, metabolism and translation, Phil.
Trans. R. Soc. B 366:2949-2958
Eschenmoser A (1994) Chemistry of potentially prebiological
Where did life begin?
Armen Y. Mulkidjanian (School of Physics, University of Osnabrück, D-49069
Osnabrück, Germany, and A.N. Belozersky Institute of Physico-Chemical Biology,
Moscow State University, Moscow 119992, Russia. amulkid@uos.de)
We attempted to reconstruct the ‘hatcheries’ of the first cells by combining
geochemical analysis with phylogenomic scrutiny of the inorganic ion requirements
of universal components of modern cells [4]. These ubiquitous, and by inference
primordial, proteins and functional systems show affinity to and functional
requirement for K+, Zn2+, Mn2+, and phosphate. Thus, protocells must have evolved
in habitats with a high K+/Na+ ratio and relatively high concentrations of Zn, Mn and
phosphorous compounds. Geochemical reconstruction shows that the ionic
composition conducive to the origin of cells could not have existed in marine
settings but is compatible with emissions of vapor-dominated zones of inland
geothermal systems. Under anoxic, CO2-dominated atmosphere, the elementary
composition of pools of condensed vapor at anoxic geothermal fields would
resemble the internal milieu of modern cells. Such pools would be lined with porous
silicate minerals mixed with metal sulfides and enriched in K+, Zn2+, and
phosphorous compounds.
Two types of environments relevant for the early stages of evolution can be
envisioned at primordial geothermal fields: (i) periodically wetted and illuminated
mineral surfaces that could serve as templates and catalysts for diverse abiotic
syntheses and (ii) pools and puddles of condensed geothermal vapor.
At least two continuous, abiotic sources of carbonaceous compounds would exist in
the described geothermal systems [4,5]. First, organic molecules could form upon
the hydrothermal alteration of iron-containing rocks. Second, diverse organic
molecules could be produced by abiotic photosynthesis catalyzed by ZnS and MnS
precipitates which, in addition, could catalyze photopolymerization reactions. At
mineral surfaces of primordial geothermal fields, ammonia, sulfide and phosphorous
compounds would react with organic compounds yielding aminated, sulfurated, and
phosphorylated molecules.
Each pool of condensed vapor would “harvest” substrates from its catchment area,
via geothermal streams and rain water. Only water-soluble compounds or
compounds that could be carried by water (e.g. as micelles of amphiphilic
molecules) could reach such ponds. Interaction of amphiphilic molecules with watersoluble (macro)molecules at mineral surfaces could yield the first protocells. Sulfidecontaining mineral sediments would protect the ptotocells from the UV damage [4].
Hence, a stratified system could be established within geothermal ponds where the
illuminated upper layers would be involved in the “harvesting” and production of
reduced organic compounds whereas the deeper, less productive but better
protected layers could provide shelter for the protocells. Both the light gradient and
the interlayer metabolite exchange are typical of modern stratified phototrophic
microbial communities.
Thus, anoxic geothermal fields would provide water basins with ionic composition
compatible with that of modern cells. These basins could host stratified
communities of primordial life forms for which the UV component of solar light
would serve as a photo-catalyst and a photo-selective factor.
References
[1] Mulkidjanian AY & Galperin MY (2007) Physico-chemical and evolutionary
constraints for the formation and selection of first biopolymers: Towards the
consensus paradigm of the abiogenic origin of life. Chemistry and
Biodiversity, 4:2003-2015.
[2] Mulkidjanian AY, Cherepanov DA, & Galperin MY (2003) Survival of the
fittest before the beginning of life: selection of the first oligonucleotide-like
polymers by UV light. BMC Evol Biol 3:12.
[3] Mulkidjanian AY (2009) On the origin of life in the zinc world: 1.
Photosynthesizing, porous edifices built of hydrothermally precipitated zinc
sulfide as cradles of life on Earth. Biol Direct 4:26.
[4] Mulkidjanian AY, Bychkov AY, Dibrova DV, Galperin MY, & Koonin EV (2012)
Origin of first cells at terrestrial, anoxic geothermal fields. Proc Natl Acad Sci
U S A doi: 10.1073/pnas.1117774109.
[5] Mulkidjanian AY (2011) Energetics of the first life. Origins of Life: The Primal
Self-Organisation, eds Egel H, Lankenau D-H, & Mulkidjanian AY (Springer,
Heidelberg), pp 1-33.
12:30-14:00
Lunch
2.00 pm Session 8 Closing panel discussion