A few chapters back,
we mentioned the emergence of complementary base pairing, and all
the advantages it had for Cassius. It was an extremely cool improvement
for cell metabolism, but it also created a huge genetic problem
that would have only grown worse, the more cells used it.
Each set of complementary pairs would tend
to cause the RNA chain or chains to link up with other sections of
the chain, whenever complementary sections came close together. The
result would be a tangled mess-- hard to transcribe, hard to
replicate, and prone to breakage of the sequence.
Roscoe and the Ribozymes
In fact, it was even worse than that. Since
some genes were carrying the sequence for ribozyme enzymes, what
was to prevent the main genetic material from curling up into ribozymes,
too?
To help solve these problems, cells probably
developed 'snagbuster' versions of Fred and Roscoe. These
slightly more clever chain-reading molecules would have had some
sort of leading edge that could break any complementary pairs as
they traveled along the RNA chain, so the main part of Fred or Roscoe
could transcribe or replicate a single chain .
It would have helped a little, but there
was another genetic problem we need to consider, and a better solution
for both.
The Master Copy
Up until now, we've been rather vague about cellular RNA, which
was sometimes a gene coding for protein sequences, and sometimes
an actual working chemical that was involved in cell metabolism.
In early versions of Clem and Cassius, presumably
Roscoe just replicated any RNA strands that it ran into, and the
cell coped with the results. Not a particularly efficient process,
but good enough for such early life forms.
However, as genes became consolidated into
fewer chains, it was also time for cells to become more 'professional' about
their gene management.
Ribonuclease
Up until now, we've only talked about the creation of new RNA
chains. But a healthy cell would go through different stages of growth,
and it would be very advantageous to get rid of the various enzymes
and helper chains when they were no longer needed.
Some types of RNA need to be permanent, but
others were pretty much just 'day use' molecules that
could be digested back to their original nucleotides, when their
task was over.
It would have been very beneficial to 'mark' the main
genetic chain in some way, so cells could digest the temporary RNA
chains, without harming the main genetic RNA.
Faster Evolution
There was also an evolutionary advantage
to reducing clutter within the genetic material.
The earliest cells probably had several copies
of each gene. So when a new, improved gene made its appearance, it
would have had only a limited impact within the cell, since the old
genes were also still present.
If cells could switch to just one 'master copy' of the
genetic chain, the impact of any genetic change would be much more
thorough. Any improved genes would improve the cell completely and
immediately .
Master Marker
How could cells 'mark' the main genetic material, so
it could be treated differently from plain old metabolic RNA? Probably
the easiest method was to make a chemical change of some kind in
the chain itself.
RNA is built from three different types of
molecules-- the nucleic acids, ribose sugars, and phosphate.
Switching to a different set of nucleic acids would have been extremely
hard to arrange, and the phosphate bonds were far too simple to change.
So what was left was the ribose.
Deoxy Roscoe
The switch to the 'master chain' may have started with
a mutant form of Roscoe that included an enzyme (probably a ribozyme)
which removed an oxygen from the ribose, as it added each new nucleotide.
It would replicate RNA chains just like a regular Roscoe, but the
product would be DNA rather than RNA .
The bad news was that the new DNA molecules
were useless as ribozymes, since DNA is somewhat more rigid than
RNA, and the molecules wouldn't have been able to bend into
their enzymatic shape so easily. However, the good news was that
the added stiffness made them much better as genetic chains, since
they wouldn't curl up into ribozymes.
That means that a regular Fred would have
an easier time converting them to proteins, and a regular Roscoe
would have an easier time reading them, and converting them back
to a functional RNA enzyme.
The differences between DNA and RNA are small
enough that the switch would not have required much new chemistry.
And it would have solved enough problems for the cell, that it would
have conferred an enormous selective advantage.
Intermediate Molecules
If cells were not able to make the
evolutionary leap from RNA
to DNA in one step, they may have
used some sort of intermediary molecule,
to act as the first ‘master
chain’ genes that were different from the functional forms
of RNA.
One possibility for
that role is methyl-RNA
, which is a more stable form of RNA that
is less prone
to chain breakage. It is
not as capable of forming ribozymes, but
it makes a much better
genetic chain than RNA itself .
The Double Helix
Remember DNA? The subject of this book? Well,
it finally has appeared!
For the moment, we only have a single strand
of it. But eventually, some clever cell managed to protect it with
a set of complementary base pairs. The result was the well known
double helix, with all the nucleotides snug in the center of the
molecule, and no risk of tangling at all.
DNA chains are chemically much more stable
than RNA, with chains that are much stronger. They are more resistant
to chemical attack, since the more reactive nucleic acids are snug
in the center, surrounded by a relatively inert wrapping of ribose
and phosphates.
The double helix of DNA also encodes its
genetic information in a redundant form, which is much easier to
maintain and repair.
What that means is that there would have
been a huge genetic advantage for any Cassius that could convert
its RNA genes into a separate 'master copy' stored in
DNA form, and then replicate them back to mRNA, as needed.
DNA is positively such a cool molecule that
it's a shame that we delayed so long in seeing it.
DNA and RNA Maintenance
The DNA chain is very similar to RNA, so
most of the enzymes that cells had previously developed for replicating
and maintaining DNA genes would have worked fine on DNA as well,
with only minor modifications. The process of switching from RNA
as the primary genetic carrier to DNA would have required some new
enzymes and new processes, but nothing that was nearly as dramatic
as the previous steps of genetic evolution that we've described.
At some point, the uridine used in RNA was
methylated and changed to thymidine. There is no strong evidence
for when or why that happened. It may possibly be an artifact of
two different strains of Cassius that each developed a portion of
the DNA/RNA system, and then later merged. It may have been helpful
in some early transition period, or it may have arisen millions of
years later, for some other reason.
When Did DNA Appear?
Well, now it's time to admit to some literary license. Delaying
the appearance of DNA may have been a little sadistic, and it's
possible that DNA first appeared much earlier, perhaps even during
the days of Caleb and Cassius.
Back when 'helper chains' first appeared, Caleb had a
management problem-- since it needed to replicate those chains,
but not transcribe them.
We talked earlier about using a 'header' sequence to
mark the chains, and that probably was the first solution-- since
it also provided a 'landing site' for Fred and/or Roscoe.
However, it's possible some version of Caleb may have accomplished
the same thing by storing the protein-coding genetic chains as DNA,
and the helper chains as RNA. If it then had a Fred that only read
DNA, and Roscoes that replicated both DNA and RNA, it would have
been all set. Its Fred would avoid accidental protein transcriptions
from the RNA chains, and Roscoe (most likely in two different versions)
would keep the genetic chains and helper chains in stock.
If that didn't happen, there would have been increasing pressure
for cells to switch to DNA, after the appearance of ribozymes. Since
their very structure depended on many complementary stretches, they
would have been particularly tangle-producing. Any cells that could
switch the main ribozyme genes to a more rigid form would have gained
a serious advantage.
Of course, locking the genetic material into
a double helix was a drastic step, and it's also possible that
there was a long period of plain old RNA chemistry (that is the gist
of the 'RNA world' theory). Its appearance certainly
would have been easier if there were already operons, gene ID, and
cells with sophisticated metabolisms.
Unfortunately, there's no sure way to know when DNA appeared.
By the time it made the scene, organisms were growing more and more
complex, and it's not easy to sort through all of the evolutionary
possibilities and affix a specific order to each improvement.
The Star of the Show
We could write much more about the DNA double
helix and its chemistry, but this is an area that has already been
well explored by other authors.
It is rather an anticlimax to treat the entry
of DNA with so little fanfare, but at least we will make up for it,
by devoting the rest of the book to its quirks and personality.
In fact, it's time to start looking at some of the odder aspects
of modern DNA, and why they are important.
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