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ScienceWeek
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
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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
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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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