It is suggested that the simpler
TNA may have led the development of RNA and DNA. I do not think that this particularly makes
the problem of discovering the pathway to manufacturing life any easier except
to confirm the value of general principals with the related molecules.
The problem itself is huge
although the good news is that it is clear that the living foundational cells
are readily shipped across space itself implying that we have had all of the
age of the universe to both solve the problem and then distribute the solution
into every nook and cranny. The mere
fact that living cells exist deep in the Earth’s crust informs of this.
Terra almost certainly began with
a full palette of beginning organisms to kick it all off. Proving it of course is the problem until we
land on our more live forgiving planets and check them out. I am sure that even Mars will have ample
surprises in this regard.
I also think that a concerted
effort can wring out a fairly decent protocol for the formation of complex
molecules in general and from which the useful selection could emerge and
continue on. One needs to recall that we
are buried in the mass produced by the successful version and that others were
subsumed long ago.
Did an earlier genetic molecule predate DNA and RNA
by Richard Harth for the Biodesign Institute
In the chemistry of the living world, a pair of nucleic acids-DNA and
RNA-reign supreme. As carrier molecules of the genetic code, they provide all
organisms with a mechanism for faithfully reproducing themselves as well as
generating the myriad proteins vital to living systems.
Yet according to John Chaput, a researcher at the Center for
Evolutionary Medicine and Informatics, at Arizona State University's Biodesign
Institute, it may not always have been so.
Chaput and other researchers studying the first tentative flickering of
life on earth have investigated various alternatives to familiar genetic
molecules. These chemical candidates are attractive to those seeking to unlock
the still-elusive secret of how the first life began,
as primitive molecular forms may have more readily emerged during the planet's
prebiotic era.
One approach to identifying molecules that may have acted as genetic
precursors to RNA and DNA is to examine other nucleic acids that differ
slightly in their chemical composition, yet still possess critical
properties of self-assembly and replication as well as the ability to fold into
shapes useful for biological function.
According to Chaput, one interesting contender for the role of early
genetic carrier is a molecule known as TNA, whose arrival on the primordial
scene may have predated its more familiar kin. A nucleic acid similar in form
to both DNA and RNA, TNA differs in the sugar component of its structure, using
threose rather than deoxyribose (as in DNA) or ribose (as in RNA) to compose
its backbone.
In an article released online in the journal Nature Chemistry, Chaput
and his group describe the Darwinian evolution of
functional TNA molecules from a large pool of random sequences. This is the
first case where such methods have been applied to molecules other than DNA and
RNA, or very close structural analogues thereof.
Chaput says "the most important finding to come from this work is
that TNA can fold into complex shapes that can bind to a desired target with
high affinity and specificity". This feature suggests that in the future
it may be possible to evolve TNA enzymes with functions required to sustain
early life forms.
Nearly every organism on earth uses DNA to encode chunks of genetic
information in genes, which are then copied into RNA. With the aid of
specialized enzymes known as polymerases, RNA assembles amino acids to form
essential proteins.
Remarkably, the basic functioning of the genetic code remains the
same, whether the organism is a snail or a senator, pointing to a common
ancestor in the DNA-based microbial life already flourishing some 3.5 billion
years ago.
Nevertheless, such ancestors were by this time quite complex, leading
some scientists to speculate about still earlier forms of self-replication.
Before DNA emerged to play its dominant role as the design blueprint for life,
a simpler genetic world dominated by RNA may have prevailed.
The RNA world hypothesis as it's known alleges that ribonucleic acid
(RNA) acted to store genetic information and catalyze chemical reactions much
like a protein enzyme, in an epoch before DNA, RNA and proteins formed the
integrated system prevalent today throughout the living world.
While the iconic double helix of DNA is formed from two complimentary
strands of nucleotides, attached to each other by base pairing in a helical
staircase, RNA is single-stranded. The two nucleic acids DNA and RNA are named
for the type of sugar complex that forms each molecule's sugar-phosphate
backbone-a kind of molecular thread holding the nucleotide beads together.
Could a simpler, self-replicating molecule have existed as a precursor
to RNA, perhaps providing genetic material for earth's earliest organisms?
Chaput's experiments with the nucleic acid TNA provide an attractive case.
To begin with, TNA uses tetrose sugars, named for the four-carbon ring
portion of their structure. They are simpler than the five-carbon pentose
sugars found in both DNA and RNA and could assemble more easily in a prebiotic
world, from two identical two-carbon fragments.
This advantage in structural simplicity was originally thought to be an
Achilles' heel for TNA, making its binding behavior incompatible with DNA and
RNA. Surprisingly, however, research has now shown that a single strand of TNA
can indeed bind with both DNA and RNA by Watson-Crick base pairing-a fact of
critical importance if TNA truly existed as a transitional molecule capable of
sharing information with more familiar nucleic acids that would eventually come
to dominate life.
In the current study, Chaput and his group use an approach known as
molecular evolution to explore TNA's potential as a genetic biomolecule. Such work draws
on the startling realization that fundamental Darwinian properties-self-replication,
mutation and selection-can operate on non-living chemicals.
Extending this technique to TNA requires polymerase enzymes that are
capable of translating a library of random DNA sequences into TNA. Once such a
pool of TNA strands has been generated, a process of selection must
successfully identify members that can perform a given function, excluding the
rest.
As a test case, the team hoped to produce through molecular evolution,
a TNA strand capable of acting as a high-specificity, high-affinity binding
receptor for the human protein thrombin.
They first attempted to demonstrate that TNA nucleotides could attach
by complementary base pairing to a random sequence of DNA, forming a hybrid
DNA-TNA strand. A DNA polymerase enzyme assisted the process.
Many of the random sequences, however, contained repeated sections of
the guanine nucleotide, which had the effect of pausing the transcription of
DNA into TNA. Once random DNA libraries were built excluding guanine, a high
yield of DNA-TNA hybrid strands was produced.
The sequences obtained were 70 nucleotides in length, long enough
Chaput says, to permit them to fold into shapes with defined binding sites. The
DNA-TNA hybrids were then incubated with the target molecule thrombin.
Sequences that bound with the target were recovered and amplified
through PCR. The DNA portion was removed and used as a template for
further amplification, while the TNA molecules displaying high-affinity, high
specificity binding properties were retained.
Additionally, the binding affinity of the evolved and selected TNA
molecules was tested against two other common proteins, for which they
displayed no affinity, strengthening the case that a highly specific binding
molecule had resulted from the group's directed evolution procedure.
Chaput suggests that issues concerning the prebiotic synthesis of
ribose sugars and the non-enzymatic replication of RNA may provide
circumstantial evidence of an earlier genetic system more readily produced
under primitive earth conditions.
Although solid proof that TNA acted as an RNA precursor in the
prebiotic world may be tricky to obtain, Chaput points to the allure of this
molecule as a strong candidate, capable of storing information,
undergoing selectionprocesses and
folding into tertiary structures that can perform complex functions. This
result provides the motivation to explore TNA as an early genetic system.
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