Biology
encodes information in DNA and RNA, which are complex molecules finely tuned to
their functions. But are they the only way to store hereditary molecular
information? Some scientists believe life as we know it could not have existed
before there were nucleic acids, thus understanding how they came to exist on
the primitive Earth is a fundamental goal of basic research.
Using
sophisticated computational methods, scientists explored the "chemical
neighbourhood" of nucleic acid analogues. Surprisingly, they found well
over a million variants, suggesting a vast unexplored universe of chemistry
relevant to pharmacology, biochemistry and efforts to understand the origins of
life. The molecules revealed by this study could be further modified to gives
hundreds of millions of potential pharmaceutical drug leads.
Nucleic
acids were first identified in the 19th century, but their composition,
biological role and function were not understood by scientists until the 20th
century. The discovery of DNA's double-helical structure by Watson and Crick in
1953 revealed a simple explanation for how biology and evolution function. All
living things on Earth store information in DNA, which consists of two polymer
strands wrapped around each other like a caduceus, with each strand being the
complement of the other.
When
the strands are pulled apart, copying the complement on either template results
in two copies of the original. The DNA polymer itself is composed of a sequence
of "letters," the bases adenine (A), guanine (G), cytosine (C) and
thymine (T), and living organisms have evolved ways to make sure during DNA
copying that the appropriate sequence of letters is almost always reproduced.
The sequence of bases is copied into RNA by proteins, which then is read into a
protein sequence. The proteins themselves then enable a wonderland of
finely-tuned chemical processes which make life possible.
Small
errors occasionally occur during DNA copying, and others are sometimes
introduced by environmental mutagens. These small errors are the fodder for
natural selection: some of these errors result in sequences which produce
fitter organisms, though most have little effect, and many even prove lethal.
The ability of new sequences to allow their hosts to better survive is the
"ratchet" which allows biology to almost magically adapt to the
constantly changing challenges the environment provides.
This
is the underlying reason for the kaleidoscope of biological forms we see around
us, from humble bacteria to tigers, the information stored in nucleic acids
allows for "memory" in biology. But are DNA and RNA the only way to
store this information? Or are they perhaps just the best way, discovered only
after millions of years of evolutionary tinkering?
"There
are two kinds of nucleic acids in biology, and maybe 20 or 30 effective nucleic
acid-binding nucleic acid analogues. We wanted to know if there is one more to
be found or even a million more. The answer is, there seem to be many, many
more than was expected," says professor Jim Cleaves of ELSI.
Though
biologists don't consider them organisms, viruses also use nucleic acids to
store their heritable information, though some viruses use a slight variant on
DNA, RNA, as their molecular storage system. RNA differs from DNA in the
presence of a single atom substitution, but overall RNA plays by very similar
molecular rules as DNA. The remarkable thing is, among the incredible variety
of organisms on Earth, these two molecules are essentially the only ones
biology uses.
Biologists
and chemists have long wondered why this should be. Are these the only
molecules that could perform this function? If not, are they perhaps the best,
that is to say, other molecules could play this role, and perhaps biology tried
them out during evolution?
The
central importance of nucleic acids in biology has also long made them drug
targets for chemists. If a drug can inhibit the ability of an organism or virus
to pass its knowledge of how to be infectious on to offspring, it effectively
kills the organisms or virus. Mucking up the heredity of an organism or virus
is a great way to knock it dead. Fortunately for chemists, and all of us, the
cellular machinery which manages nucleic acid copying in each organism is
slightly different, and in viruses often very different.
Organisms
with large genomes, like humans, need to be very careful about copying their hereditary
information and thus are very selective about not using the wrong precursors
when copying their nucleic acids. Conversely, viruses, which generally have
much smaller genomes, are much more tolerant of using similar, but slightly
different molecules to copy themselves.
Since
most scientists believe the basis of biology is heritable information, without
which natural selection would be impossible, evolutionary scientists studying
the origins of life have also focused on ways of making DNA or RNA from simple
chemicals that might have occurred spontaneously on primitive Earth. Once
nucleic acids existed, many problems in the origins of life and early evolution
would make sense. Most scientists think RNA evolved before DNA, and for subtle
chemical reasons which make DNA much more stable than RNA, DNA became life's
hard disk.
However,
research in the 1960s soon split the theoretical origins field in two: those
who saw RNA as the simple "Occam's Razor" answer to the
origins-of-biology problem and those who saw the many kinks in the armour of
RNA's abiological synthesis. RNA is still a complicated molecule, and it is possible
structurally simpler molecules could have served in its place before it arose.
Examining
all of these basic questions, which molecule came first, what is unique about
RNA and DNA, all at once by physically making molecules in the laboratory, is
difficult. On the other hand, computing molecules before making them could
potentially save chemists a lot of time.
See:
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)
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