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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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