[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
http://scienceweek.com/2005/sw050325-1.htm
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
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Related Material:
ORIGIN OF LIFE: ON TRANSITIONS FROM NONLIVING TO LIVING MATTER
The following points are made by S. Rasmussen et al (Science 2004
303:963):
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
(2-5).
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
--------------------------------
ORIGIN OF LIFE: MODELS OF PRIMITIVE CELLULAR COMPARTMENTS
The following points are made by M.M. Hanczyc et al (Science 2003
302:618):
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
conditions.
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
efficient.
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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