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Origin of Life Theories - Latest Problems

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Early theories of the origin of life centered on the ability of a reducing atmosphere of the prebiotic earth to instigate formation of amino acids, and subsequently assembly of proteins. Stanley Miller demonstrated in 1953 that mixtures of reducing gases, thought to be present in the primordial earth, when subjected to electrical discharges, produced many organic compounds, including several amino acids. Years later, a meteor which landed in Murchison, Australia, was shown to contain the same organic compound and amino acids in roughly the same proportion as those generated through the Miller experiments.

Homochirality

Although the Miller experiments and the Murchison meteor suggested that organic molecules could be synthesized in the absence of life, many questions and problems arose. Although simple proteins could be produced by laboratory manipulations of amino acidbuilding blocks, no model or method of self replication of proteins could be found. In addition, the amino acids which compose all forms of life are exclusively of the "left-handed" variety (L- amino acids).

Those produced in the Miller experiments and found in the Murchison meteor are both L- and R- amino acids. No model could be proposed which would explain inclusion of only one form of amino acids to the exclusion of the other, without the aid of RNA's, in the form of ribosomal RNA (rRNA), transfer RNA ( tRNA), and messenger RNA ( mRNA). All models would require the spontaneous evolution of both RNA's and proteins simultaneously.

In addition, specific proteins are required in combination with rRNA in order for other proteins to be synthesized. This dilemma has led to statements, such as that of Leslie Orgel, "And so, at first glance, one might have to conclude that life could never, in fact, have originated by chemical means."

RNA World

To try to avoid the overwhelming problems associated with the self replication of proteins, Carl Woese, Francis Crick, and Leslie Orgel proposed RNA as the original building blocks of life. They proposed that self-replicating RNA could code for proteinsand eventually evolve into DNA, because of DNA's superior intrinsic stability. Experiments by several scientists have demonstrated the ability of RNA's to catalyze chemical reactions, similar to that seen by enzymes (which are proteins). But could RNAitself have been synthesized and replicated by chemical means on the prebiotic earth?

Problems getting the building blocks

Juan Or— discovered in 1961 that the nucleic acid base adenine could be synthesized in a mixture of hydrogen cyanide and ammonia. Since then, scientists have shown that the remaining nucleic acid bases, guanine, uracil, and cytosine, could be synthesized from mixtures of hydrogen cyanide, cyanogen, and cyanoacetylene. When the nucleic acid bases are combined with the sugar ribose and phosphate, nucleotides form, which in the presence of an appropriate catalyst, form random strands of RNA. The spontaneous formation of a self-replicating RNA (which acts as a catalyst for replication of itself) ensures perpetuation of the RNA, according to the theory.

It is at this point that the theory encounters major problems. First, there is no mechanism for the synthesis of ribose in the absence of enzymes. All chemical reactions which synthesize ribose, produce it as a very minor product. The major products are other sugars, which combine with nucleic acids to form products which inhibit RNA synthesis and replication. In addition, any ribose formed is racemic, that is, both left- and right-handed. Only right-handed ribose can be used to form nucleotides. Left-handed ribose interfers with RNA synthesis.

The next major problem is that nucleotides do not form under prebiotic conditions. If the phosphate is left out, purine nucleosides (adenine and guanine) will form under these conditions, but no pyrimidine nucleosides (cytosine and uracil) form. Even if a method for formation of pyrimidine nucleosides could be found, the combination of nucleosides with phosphate under prebiotic conditions produces not only nucleotides, but other products which interfere with RNA polymerization and replication.

In order to get around the problems of nucleotide formation, scientists have proposed that certain minerals may serve as catalysts for specific formation of only proper nucleotides. To date, no such catalysts have been found.

Even if nucleotides could be formed by some method, both right- and left-handed versions would be formed. When both right- and left-handed nucleotides are added to RNA templates, replication is inhibited.

Which came first?

Beyond the problems of nucleotide formation are still more problems regarding how RNA polymers might replicate in the absence of proteins. The addition of nucleotides will produce a complementary strand of RNA. However, there is, at present, no explanation for duplication of the original RNA polymer from the complementary strand, in the absence of enzymes.

A key component of the RNA world hypothesis, adenine, has its own problems:

1. Adenine synthesis requires HCN concentrations of at least 0.01 M. It is completely unreasonable to expect these concentrations on the prebiotic earth.
2.Adenine is susceptible to hydrolysis (the half-life for deamination at 37°C, pH 7, is about 80 years). Therefore, no adenine would ever be expected to accumulate in any kind of "prebiotic soup."
3.The adenine- uracil interaction is weak and nonspecific, and, therefore, would never be expected to function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup."

Similar problems apply to the abiotic synthesis of cytosine:

1.Cytosine has never been found in any meteorites.
2.Cytosine is not produced in electric spark discharge experiments using simulated "early earth atmosphere."
3.Synthesis based upon cyanoacetylene requires the presence of large amounts of methane and nitrogen, however, it is unlikely that significant amounts of methane were present at the time life originated.
4.Synthesis based upon cyanate is problematical, since it requires concentrations in excess of 1 M (molar). When concentrations of 0.1 M (still unrealistically high) are used, no cytosine is produced.
5.Synthesis based upon cyanoacetaldehyde and urea suffers from the problem of deamination of the cytosine in the presence of high concenrations of urea (low concentrations produce no cytosine). In addition, cyanoacetaldehyde is reactive with a number of prebiotic chemicals, so would never attain reasonable concentrations for the reaction to occur. Even without the presence of other chemicals, cyanoacetaldehyde has a half-life of only 31 years in water.
6.Cytosine deaminates with an estimated half-life of 340 years, so would not be expected to accumulate over time.
7.Ultraviolet light on the early earth would quickly convert cytosine to its photohydrate and cyclobutane photodimers (which rapidly deaminate).

According to Robert Shapiro, a prominent origin of life researcher, the spontaneous formation of a nucleic acid replicator is a "very improbable event." this is because the mixture of amino acids the Murchison meteorite show that there are many classes of prebiotic substances that would disrupt the necessary structural regularity of any replicator.

In addition, all current synthesis schemes require concentration of reactants by a factor of at least 100,000. Robert Shapiro, in his analysis of the "drying lagoon" scenario said:

"If today's Earth may be taken as a model for the early one, then, cases of extreme lagoon concentration (to the extent needed to concentrate a solute by 105) are rare or nonexistent. This mechanism cannot be considered as a source that could stock a global ocean with a particular chemical."

Conclusion

It is becoming increasingly apparent from over 40 years of research in the field, that the RNA model will never adequately explain life's origin. Increasingly, investigators are looking at alternative models, including pyranosyl RNA and peptidenucleic acid polymers. These models, too, have major problems, which are probably insurmountable.

The current trend in origin of life research is to look for simpler, pre-RNA molecules to serve as genetic material. These models will suffer the same fate as all the rest, namely, the incredible increase in information content required to produce self-replication is not possible in the time frame in which it was supposed to have occurred. The simpler the first step, the more likely it is to occur, but the harder it is to get from step one to step two.

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