[Paleopsych] Science Week: Origin of Life: In Search of the Simplest Cell

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Origin of Life: In Search of the Simplest Cell

    The following points are made by Eörs Szathmary (Nature 2005 433:469):
    1) In investigating the origin of life and the simplest possible life
    forms, one needs to enquire about the composition and working of a
    minimal cell that has some form of metabolism, genetic replication
    from a template, and boundary (membrane) production.
    2) Identifying the necessary and sufficient features of life has a
    long tradition in theoretical biology. But living systems are products
    of evolution, and an answer in very general terms, even if possible,
    is likely to remain purely phenomenological. Going deeper into
    mechanisms means having to account for the organization of various
    processes, and such organization has been realized in several
    different ways by evolution. Eukaryotic cells (such as those from
    which we are made) are much more complicated than prokaryotes (such as
    bacteria), and eukaryotes harbor organelles that were once free-living
    bacteria. A further complication is that multicellular organisms
    consist of building blocks -- cells -- that are also alive. So aiming
    for a general model of all kinds of living beings would be fruitless;
    instead, such models have to be tied to particular levels of
    biological organization.
    3) Basically, there are two approaches to the "minimal cell": the
    top-down and the bottom-up. The top-down approach aims at simplifying
    existing small organisms, possibly arriving at a minimal genome. Some
    research to this end takes Buchnera, a symbiotic bacterium that lives
    inside aphids, as a rewarding example. This analysis is complemented
    by an investigation of the duplication and divergence of genes.
    Remarkably, these approaches converged on the conclusion that genes
    dealing with RNA biosynthesis are absolutely indispensable in this
    framework. This may be linked to the idea of life's origins in an "RNA
    world", although such an inference is far from immediate.
    4) Top-down approaches seem to point to a minimum genome size of
    slightly more than 200 genes. Care should be taken, however, in
    blindly accepting such a figure. For example, although some gene set A
    and gene set B may not be common to all bacteria, that does not mean
    that (A and B) are dispensable. It may well mean that A or B is
    essential, because the cell has to solve a problem by using either A
    or B. Only experiments can have the final word on these issues.
    5) A top-down approach will not take us quite to the bottom, to the
    minimal possible cells in chemical terms. All putative cells, however
    small, will have a genetic code and a means of transcribing and
    translating that code. Given the complexity of this system, it is
    difficult to believe, either logically or historically, that the
    simplest living chemical system could have had these components.
    6) The bottom-up approach aims at constructing artificial chemical
    supersystems that could be considered alive. No such experimental
    system exists yet; at least one component is always missing.
    Metabolism seems to be the stepchild in the family: what most
    researchers in the field used to call metabolism is usually a trivial
    outcome of the fact that both template replication and membrane growth
    need some material input. This input is usually simplified to a
    conversion reaction from precursors to products.
    Nature http://www.nature.com/nature
    Related Material:
    The following points are made by S. Rasmussen et al (Science 2004
    1) All life forms are composed of molecules that are not themselves
    alive. But in what ways do living and nonliving matter differ? How
    could a primitive life form arise from a collection of nonliving
    molecules? The transition from nonliving to living matter is usually
    raised in the context of the origin of life. But some researchers(1)
    have recently taken a broader view and asked how simple life forms
    could be synthesized in the laboratory. The resulting artificial cells
    (sometimes called protocells) might be quite different from any extant
    or extinct form of life, perhaps orders of magnitude smaller than the
    smallest bacterium, and their synthesis need not recapitulate life's
    actual origins. A number of complementary studies have been steadily
    progressing toward the chemical construction of artificial cells
    2) There are two approaches to synthesizing artificial cells. The
    top-down approach aims to create them by simplifying and genetically
    reprogramming existing cells with simple genomes. The more general and
    more challenging bottom-up approach aims to assemble artificial cells
    from scratch using nonliving organic and inorganic materials.
    3) Although the definition of life is notoriously controversial, there
    is general agreement that a localized molecular assemblage should be
    considered alive if it continually regenerates itself, replicates
    itself, and is capable of evolving. Regeneration and replication
    involve transforming molecules and energy from the environment into
    cellular aggregations, and evolution requires heritable variation in
    cellular processes. The current consensus is that the simplest way to
    achieve these characteristics is to house informational polymers (such
    as DNA and RNA) and a metabolic system that chemically regulates and
    regenerates cellular components within a physical container (such as a
    lipid vesicle).
    4) Two recent workshops(1) reviewed the state of the art in artificial
    cell research, much of which focuses on self-replicating lipid
    vesicles. David Deamer (Univ. of California, Santa Cruz) and Pier
    Luigi Luisi (ETH Zurich) each described the production of lipids using
    light energy, and the template-directed self-replication of RNA within
    a lipid vesicle. In addition, Luisi demonstrated the polymerization of
    amino acids into proteins on the vesicle surface, which acts as a
    catalyst for the polymerization process. The principal hurdle remains
    the synthesis of efficient RNA replicases and related enzymes entirely
    within an artificial cell. Martin Hanczyc (Harvard Univ.) showed how
    the formation of lipid vesicles can be catalyzed by encapsulated clay
    particles with RNA adsorbed on their surfaces. This suggests that
    encapsulated clay could catalyze both the formation of lipid vesicles
    and the polymerization of RNA.
    References (abridged):
    1. http://www.ees.lanl.gov/protocells
    2. C. Hutchinson et al., Science 286, 2165 (1999)
    3. M. Bedau et al., Artif. Life 6, 363 (2000)
    4. J. Szostak et al., Nature 409, 387 (2001)
    5. A. Pohorille, D. Deamer, Trends Biotechnol. 20, 123 (2002)
    Science http://www.sciencemag.org
    The following points are made by M.M. Hanczyc et al (Science 2003
    1) The bilayer membranes that surround all present-day cells and act
    as boundaries are thought to have originated in the spontaneous
    self-assembly of amphiphilic molecules into membrane vesicles (1-5).
    Simple amphiphilic molecules have been found in meteorites and have
    been generated under a wide variety of conditions in the laboratory,
    ranging from simulated ultraviolet irradiation of interstellar ice
    particles to hydrothermal processing under simulated early Earth
    2) Molecules such as simple fatty acids can form membranes when the pH
    is close to the pK[sub-a] (K[sub-a] is the acid dissociation
    equilibrium constant) of the fatty acid carboxylate group in the
    membrane (3). Hydrogen bonding between protonated and ionized
    carboxylates may confer some of the properties of more complex lipids
    with two acyl chains, thus allowing the formation of a stable bilayer
    phase. Fatty acid vesicles may be further stabilized (to a wider range
    of pH and even to the presence of divalent cations) by the admixture
    of other simple amphiphiles such as fatty alcohols and fatty acid
    glycerol esters. Recent studies have shown that saturated fatty
    acid/fatty alcohol mixtures with carbon chain lengths as short as 9
    can form vesicles capable of retaining ionic fluorescent dyes, DNA,
    and proteins (4).
    3) Vesicles consisting of simple amphiphilic molecules could have
    existed under plausible prebiotic conditions on the early Earth, where
    they may have produced distinct chemical micro-environments that could
    retain and protect primitive oligonucleotides while potentially
    allowing small molecules such as activated mononucleotides to diffuse
    in and out of the vesicle. Furthermore, compartmentalization of
    replicating nucleic acids (or some other form of localization) is
    required to enable Darwinian evolution by preventing the random mixing
    of genetic polymers, thus coupling genotype and phenotype. If
    primordial nucleic acids assembled on mineral surfaces, the question
    arises as to how they eventually came to reside within membrane
    vesicles. Although dissociation from the mineral surface followed by
    encapsulation within newly forming vesicles (perhaps in a different
    location under different environmental conditions) is certainly a
    possibility, a direct route would be more satisfying and perhaps more
    4) In summary: The clay montmorillonite is known to catalyze the
    polymerization of RNA from activated ribonucleotides. The authors
    report that montmorillonite accelerates the spontaneous conversion of
    fatty acid micelles into vesicles. Clay particles often become
    encapsulated in these vesicles, thus providing a pathway for the
    prebiotic encapsulation of catalytically active surfaces within
    membrane vesicles. In addition, RNA adsorbed to clay can be
    encapsulated within vesicles. Once formed, such vesicles can grow by
    incorporating fatty acid supplied as micelles and can divide without
    dilution of their contents by extrusion through small pores. These
    processes mediate vesicle replication through cycles of growth and
    division. The authors suggest the formation, growth, and division of
    the earliest cells may have occurred in response to similar
    interactions with mineral particles and inputs of material and energy.
    References (abridged):
    1. J. M. Gebicki, M. Hicks, Nature 243, 232 (1973)
    2. J. M. Gebicki, M. Hicks, Chem. Phys. Lipids 16, 142 (1976)
    3. W. R. Hargreaves, D. W. Deamer, Biochemistry 17, 3759 (1978)
    4. C. L. Apel, D. W. Deamer, M. N. Mautner, Biochim. Biophys. Acta
    1559, 1 (2002)
    5. P.-A. Monnard, C. L. Apel, A. Kanavarioti, D. W. Deamer,
    Astrobiology 2, 139 (2002)
    Science http://www.sciencemag.org

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