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The Science of Presumption Can Be A Beautiful Thing - Part 2


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"You stated earlier, Dr. Yardley, that this fellow Eschenmoser had made several contributions which bear on the issue being discussed. What is the other one?"

"Around 1994," said the professor, "Eschenmoser discovered a way of limiting the kinds of sugars which are synthesized during the formose reaction. Without getting into the technical details of the experiment, essentially, he replaced one of the normal intermediates of the formose reaction with a similar phosphorylated molecule, and, then, he permitted the subsequent steps of the reaction to proceed as normal."

"Excuse me," Dr. Yardley, "am I right in believing that a phosphorylated molecule is a compound to which a phosphate group has been added and which, under certain circumstances, may be capable of storing energy if particular kinds of pyrophosphate bonds are present?"

"Essentially, yes," the professor said.

"Under certain conditions, when this kind of substitution was made, the primary end product of the formose reaction was a phosphorylated derivative of ribose. This substitution process, therefore, represents a possible way of getting around the selectivity problem that arises as a result of the multiplicity of competing sugar forms which exists when one permits the formose reaction to proceed as usual."

Checking the papers in his hand before speaking, Mr. Tappin said: "In the experiment just described, Professor, wouldn't the phosphate group on the synthesized ribose derivative have to be rearranged upon completion of Eschenmoser& #146;s altered pathway for the formose reaction in order to be the same as the phosphorylated ribose that is found in normal nucleotides?"

"Yes, that's true," the professor acknowledged.

"In addition," the defense counsel observed, "doesn't the Eschenmoser experiment leave one with a slight problem of needing to explain how one is going to bring about this substitution process under prebiotic conditions when, presumably, there is no Archean era counterpart to Albert Eschenmoser, or his lab assistants, who would be available to make the substitution? Moreover, doesn't all of this assume that the closely related phosphorylated molecule which is to be substituted for the normal intermediate of the ribose-forming reaction is going to be available to be inserted into the formose reaction at just the right moment?"

"This would appear to be the case," replied the professor.

"Would you agree, Dr. Yardley," queried the lawyer, "that although there has been some success in synthesizing adenosine and guanosine nucleosides when purified mixtures of ribose and purine bases have been heated in the presence of certain inorganic salts, these same successes are not observed with pyrimidine nucleosides, such as uracil and cytosine, under any conditions which could be considered to be plausible in the Archean era?"

"Yes, that is correct," the professor confirmed.

"Apparently, then," summarized Mr. Tappin, "at the present time there is no known, plausible pathways under prebiotic conditions for synthesizing more than half of the five nucleosides which are fundamental to the storage of genetic information in both DNA and RNA. Is this more or less the state of things in evolutionary theory, Professor?"

"More or less," Dr. Yardley stated.

"To further confuse matters," added the lawyer, "even in the case of the synthesis of the nucleic purine bases, adenine and guanine, one is likely to find other kinds of bases such as hypoxanthine, diaminopurine and a variety of related molecules accompanying the synthesis of the specific purine bases that are important to the nucleic acids which occur in living organisms. So, wouldn't you agree, Dr. Yardley, that, here too, the Archean era, through natural chemical processes, is likely to have generated a variety of cross-linked polymers that somehow would have to be selected against in order to work toward the kind of life form which resembles that with which we are familiar today?"

"Yes, I would agree with this," Dr. Yardley said.

"Would you agree, Professor," asked Mr. Tappin, "that all of the problems which have been discussed in relation to the formation of nucleosides would carry over into the formation of nucleotides during which a phosphate component is added to the nucleoside combination of ribose and one of the five nucleic bases? In other words, wouldn't there be a substantial array of abnormal nucleotides consisting of various pentoses other than ribose, as well as forms of ribose other than the right-handed optical isomer of beta-ribofuranose, and, if this is the case, wouldn't these interfere with both catalytic processes as well as RNA replication?"

"Yes, one might have to assume this may have been the case," affirmed the professor.

"Dr. Yardley, beside the abnormal nucleotides which would form as a result of the presence of different pentoses, ribose forms and optical isomers, wouldn't there also be an assortment of abnormal phosphate bonds which could arise? In other words, isn't it true that beyond the normal, 5-prime- phosphate bond which occurs during one of the stages leading to the formation of the sorts of nucleic acid found in living organisms, one also might obtain problematic bonding arrangements such as: 2-prime- phosphate bonds; or, 3-prime-phosphate bonds; or, 2-prime-3 prime-cyclic phosphates; or, 2-prime-5 prime- biphosphate; or, 3-prime-5-prime-biphosphates?"

"This is true," affirmed the professor.

"Would you also agree, Dr. Yardley," added Mr. Tappin, "that, in the light of current knowledge, the Archean era is much more likely to have consisted of such a mixture of phosphate bonds, pentoses, different forms of ribose, as well as a racemic aggregation of optical isomers, rather than having consisted of the purified solutions with which laboratory experiments are run?"

"Yes," said the professor.

"In addition, Dr. Yardley, would you agree that despite all the problems which exist in relation to the formation of ribonucleic acids, nevertheless, RNA is more easily synthesized than is deoxyribonucleic acid? In fact, can we not say that one of the considerations which led to the rise of the RNA-world hypothesis was rooted in the way RNA is much more easily synthesized than is DNA?"

"The answer to both of your questions is 'yes'," responded the professor.

"In your opinion, Dr. Yardley," queried the defense counsel, "even if much of the RNA-world hypothesis turned out to be true, wouldn't evolutionary theorists still be faced with the problem of proposing a plausible prebiotic mechanism for the synthesis of DNA?"

"I believe this is so, yes," the professor admitted.

"On the other hand," Mr. Tappin indicated, "although RNA is more easily synthesized than DNA, DNA is much less susceptible to hydrolysis, or breakdown in an aqueous environment, than is the case with RNA. If my information is correct, isn't it true, Professor, that at room temperature RNA breaks down at a rate which is roughly 100 times faster than does DNA, and, within certain limits, this differential rate of breakdown climbs somewhat with increases in temperature above room temperature?"

"This is basically right," stated the professor, "except that depending on the temperatures you are talking about, both DNA and RNA tend to decompose more readily at elevated temperatures."

"Dr. Yardley, assuming my understanding of things is right, if one starts with a single polymer or chain of RNA in solution, a complementary strand easily can be generated by adding free, non-polymerized nucleotides to the solution, since, subsequently, these free nucleotides will line up opposite their pairing partner on the original RNA strand - that is, uracil with adenine and cytosine with guanine. Moreover, the original strand and its complement will form, in the absence of enzymes, a double helical structure by means of the spontaneous hydrogen bonding of these Watson-Crick pairings. Is all of this correct?"

"Yes," the professor replied.

"Yet," the defense counsel stipulated, "the foregoing scenario assumes, does it not, Professor, that all of the free nucleotides which are being added to form the complementary strand must exhibit the same optical properties or handedness as the original strand of RNA?"

"That's correct," Dr. Yardley affirmed.

"In other words," indicated the lawyer, "if one places both left-handed and right-handed optical isomers of various free nucleotides into the solution, then the presence of both left- and right-handed isomeric forms of the nucleotides will inhibit the formation of a complementary strand capable of bonding with the original strand through Watson-Crick pairings. Isn't this so, Dr. Yardley?"

"Yes, it is," acknowledged the professor.



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