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Origin of Life

After Louis Pasteur demonstrated that living things, even microscopic living things, arose directly from prior living things, the question of the origin of the first living things became much more important.

 It is not known how life originated--there are no time machines and fossils of pre-cells either do not exist or are difficult to interpret. Even if life is generated someday in a lab through a series of chemical reactions, there would be no proof that the first living things evolved through the same sequence of chemical reactions. As a result, science will never be able to prove how life started. Scientists can, however, study what scenarios are possible given the conditions of the early earth and determine if the characteristics of modern cells offer support for any of the models. The question boils down to this: over the course of a few hundred million years, could the sum of all the chemical reactions which occurred on the early earth (in its oceans, its continually flooded tidal zones, its subsurface, its volcanic vents, and even in the material which was bombarding it from space) produce complex aggregates of molecules which achieve the level of complexity of the most minimal forms of life? Obviously, answering this question is complicated by the facts that scientists are just beginning to appreciate the wide array of organic molecules which can be produced in the absence of life, the conditions of the early earth, the contribution to the chemistry of the early earth made by molecules found in comets and meteors, etc. Although it is easy enough to study the simplest cells alive today, these cells are more than 3.5 billion years removed from the first cells and they should not be considered as models for the simplest living things.

 Is it possible that life developed through natural processes on a lifeless earth? Charles Darwin suggested that life could have arisen chemically in some warm little pond, with all sorts of ammonia and phosphoric salts, light, heat, electricity, etc. present. (He never made this suggestion publicly, perhaps for fear of the public reaction to it.) There is a great body of accumulating evidence which suggests that many of the important steps in the origin of life could have occurred through natural processes. Although life has not been generated in a laboratory, it is unrealistic to expect that biochemists succeed in replicating all of the chemical reactions which could have occurred on an entire planet (and the surrounding solar system, given that extraterrestrial bombardment was adding organic content to earth) over a period of hundreds of millions of years, especially since this question has only be subject to experimental investigation for fifty years or so. The discoveries which have already resulted from this research (such as the catalytic properties of RNA) have already made great contributions to molecular biology and organic chemistry.

 Although science can not at present answer the question of whether life evolved (and may never be able to do so), there are simpler questions which can be asked and possibly answered.

  Is it possible that organic molecules (those complex molecules of living things) arose from simple inorganic molecules in the absence of life? Yes.

Organic molecules were once thought to exist only in living things and to have possess an "animism" or "vitalism" which could not arise without life (Joyce, 1998). Vitalists once argued that organic molecules could never be generated in a lab or, for that matter, anywhere outside a living organism. They were proven wrong. Organic molecules can be formed without life in labs and organic molecules have been detected in meteorites, comets, and several bodies of our solar system (such as the Jupiter moons Callisto and Ganymede). In other words, the organic molecules which are the the stuff of life can be found without life.

The Miller-Urey experiment (and subsequent experiments) demonstrated that all the simple organic molecules which life depends on can be synthesized using only the gases of the primitive earth's atmosphere and a source of energy. There would have been plenty of energy in a primitive earth the heat of a semimolten planet, lightning, solar radiation unfiltered by an ozone layer, etc. By simply mixing inorganic molecules and energy, the following organic molecules have been produced: all the amino acids found in living things (in addition to amino acids not found in living things), all essential sugars, triphosphate nucleotide precursors needed for the synthesis of the DNA and RNA, aldehydes, carboxylic acids, and others. These organic molecules synthesized in the absence of life could incorporate a large percentage of the available carbon. Miller found that up to 10% of all carbon atoms could be incorporated into organic molecules and up to 2% incorporated into amino acids.  In an analysis of a meteorite supported the results of the Miller-Urey experiment: both the meteorite and the experiment produced some of the same amino acids and in the same relative quantities.

Could these small organic building blocks have joined to form larger biomolecules in the absence of life? Yes.

In living organisms, small organic molecules (monomers) can not only function alone, they can bind to each other to form long chains (polymers). Can monomers join to form polymers in the absence of life? Yes. Not only can this occur in solution, there are a number of catalysts which can speed these reactions.Certain mineral surfaces (feldspar, calcite, zeolites, clays) provide sites where small organic molecules can fuse to form larger ones. The small molecules (RNA nucleotides, amino acids) absorb onto these surfaces and, since they are in close enough proximity to each other and in the right orientation, they can bond to form chains. Small proteins of over 200 amino acids have been produced and short strands of DNA and RNA (up to 50 nucleotides long).Because minerals help to catalyze polymerization reactions, the rocks of early earth could have been covered with chains of at least tens of monomer units (Joyce, 1998)

3) Can molecules replicate themselves in the absence of life? Yes, to some degree.

 Modern organisms depend on a very complex set of mechanisms to replicate their genetic code in order to reproduce. Can the replication of simple molecules occur in the absence of life? Yes. Short RNA and DNA molecules can serve as templates and replicate themselves. (One RNA has actually shown itself not only to be a template of its own replication, but a catalyst of RNA replication as well.) In 1996, a small protein (based on a protein found in yeast) was observed to replicate itself. Amines and esters can combine to form an amide which then serves as a template for other amines and esters to do the same. There are a number of organic molecules which are not found in living things which have been shown to replicate (especially vinyl homopolymers and copolymers).

4) Living organisms use certain forms of molecules (stereoisomers) and not others. Can this nonrandom selection of stereoisomers occur in the absence of life? Yes.

Living things use one form (or stereoisomer) of amino acids and sugars but not the other. Are there mechanisms which could produce such a preference? There is evidence that the form of amino acids found in living things is more likely to form spontaneously, there are clays which facilitate the formation of chains with only one form, and catalytic organic molecules are known which join only similar stereoisomers.

5)     Could organic molecules form membranous balls? Could these precells perform some activities that cells perform? Yes.

Living cells are surrounded by lipid cell membranes. Although lipids can form in the absence of life, could such lipids spontaneously form cell membrane-like structures? Yes. Lipids in solution form layers that are similar in structure and function to those of cell membranes. In solution, lipids can form spheres known as micelles, coarcervates, and microspheres. Simulations of the formation of organic molecules in the interstellar ices of comets (using UV light) form organic molecules that self-assemble into such vesicles. These vesicles can accumulate organic molecules inside themselves, increase in size, and even split once they reach a certain size. If enzymes (proteins which speed chemical reactions) are in these droplets, chemical reactions can occur. If they contain the enzyme RNA polymerase, RNA nucleotides are taken from the environment and assembled into RNA chains (Zimmer, 1995).  Organic molecules gathered from meteorites have been found to form these membranous balls in water.


6) Does RNA display the ability to serve as both a genetic code and catalyze reactions? Yes.

���� Modern cells are very complex. For example, modern cells use proteins to catalyze their chemical reactions but the synthesis of protein depends on RNA and the synthesis of RNA depends on DNA. Since the synthesis of DNA itself depends on protein, how could the first cells function without three sets of complex molecules, DNA, RNA, and protein? It is possible that the first cells existed in an RNA world in which protein and DNA did not exist. Could RNA molecules have performed the functions of proteins while simultaneously serving as the first genetic code? In modern living things, RNA is still the only molecule which functions both as a genotype (a genetic code) and phenotype (determining outward appearance many RNAs are functional by themselves and are never converted to protein). There are a number of observations which suggest that RNA was the primary functional molecule in the earliest cells.

a) Nucleotides (primarily RNA nucleotides) have very diverse roles in cells

 An analysis of modern cells suggests that RNA is central to many cellular mechanisms. RNA nucleotides (the monomers which compose the chains of RNA) are essential molecules for modern cells. The molecule which cells use for virtually all of their energy transactions (ATP) is an RNA nucleotide with additional phosphate groups added. In other words, the energy which you are using at this moment to power muscle contractions, pump ions, move cilia, cause cells to divide, etc. is being derived from ATP, an RNA nucleotide with additional phosphate groups. Most coenzymes are either modified nucleotides or can be synthesized from nucleotides.

b) RNA molecules can act as enzymes (both those found in living cells and sequences generated in the absence of life)

 Although proteins are indispensable in modern cells (for example, proteins called enzymes catalyze chemical reactions), RNA molecules can be found which perform many of the tasks done by modern proteins. In collections of random RNA sequences, some RNA molecules can be isolated which perform certain functions (such as catalyzing reactions). RNA enzymes (ribozymes) have been isolated from these random sequences that help to copy existing RNA molecules using the same reaction that proteins use in modern cells. These ribozymes can also undergo a natural selection of sorts in which researchers favor a certain type of ribozyme and over time these random sequences produced more efficient ribozymes which can catalyze the reaction hundreds to millions of times faster than the rate observed without the ribozyme (Bartel, 1993; Wright, 1997).


c) Ribozymes in modern cells can catalyze a diversity of chemical reactions

 In the early earth, could RNA ribozymes have functioned in the conversion of RNA to DNA, the conversion of RNA to protein, and the splicing of small coding units to form functional genetic messages? This is not an unreasonable hypothesis, given that RNA molecules in modern cells perform these and other reactions. RNA continues to perform diverse functions in living cells and is most active in the cellular activities that would have been the most ancient (such as the splicing of the genetic message and the synthesis of proteins).

 The reactions that modern RNA molecules isolated from living cells perform include the cutting and splicing of RNA molecules (spliceosomes, self-editing introns; Sharp, 1985; Cech, 1987; Kruger, 1982), extending the ends of chromosomes (telomerase) (Poole, 1997), the modification of the tRNAs used in protein construction (Rnase P), nucleotide insertion (Mueller, 1993), breaking triphosphate bonds for energy (srp RNA) (Jeffares, 1998) and the folding, cleavage, nucleotide modification, and assembly of ribosomal subunits (snoRNAs; Maxwell, 1995). Proteins synthesis, arguably one of the most important cellular processes, occurs at structures known as ribosomes whose RNA actually functions as a ribozyme (Steitz, 2003)


d) Ribozymes generated in the lab can catalyze a diversity of chemical reactions

 Can artificial ribozymes replicate themselves? Yes and no. Although ribozymes which perform the necessary reactions in self replication have been isolated, they do not function at the levels that a precursor to a living cell would require (Bartel, 2000). Ribozymes can recognize a primer template and attach complimentary bases to the template. The ability to join RNA nucleotides to a primer has been accomplished by different ribozymes with different structures and biochemical properties. The accuracy of the addition of complementary bases was 97% and could be increased to 99% by altering the nucleotide concentrations. One ribozyme could extend the primer by 14 nucleotides (although the ribozyme itself was 189 nucleotides) (McGuiness, 2003).

 In experiments without cells, ribozymes can be selected for out of random RNA sequences that catalyze chemical reactions such as nucleotide synthesis, forming carbon-carbon bonds, forming bonds that modern ribosomes must form during protein synthesis, and forming the bonds that modern tRNA synthetases (which are proteins) perform in protein synthesis, cleave phosphodiester bonds, act as RNA ligase, hydrolyze cyclic phosphates, phosphorylate RNA, transfer phosphate anhydride, perform acyl transfer, form amide bonds, form peptide bonds, form glycosidic bonds, and a number of other reactions (Bartel, 2000; Landweber, 1999, Ekland, 1996; Ekland, 1995. Green 1992, Illangasekare, 1995; Lohse, 1996; Tarasow, 1997; Bartel, 1993; Unrau, 1998).


How could early precells acquire additional catalytic RNA molecules? Mutations are a source of diversity in modern organisms and would have generated a diversity of RNAs in the early cells. In modern organisms, lateral transfer can also occur in which genes can move from one species into another. DNA can be exchanged between living cells and living cells can take up DNA from their environment. Viruses occasionally introduce DNA fragments from their previous host into their next host.

 Early genetic systems would have experienced a very high mutation rate and a very high lateral transfer rate. As a result, organisms as the term is currently understood did not exist since genes could be exchanged regardless of lineage. It has been proposed that the last universal common ancestor of modern organisms was more of a community of cells rather than a single cell. Lateral gene transfer may have been the primary mechanism of evolution in these earliest cells, rather than descent with modification (Woese, 1998).