I’m
re-posting chapters of my work-in-progress, The Demeaning of Life. Last winter, I did major re-writes and rearranged the order of a number
of chapters. This one, about DNA, has not been significantly altered but I’m posting
it again for the sake of continuity. Plus, it’s one of the most compelling
accounts in the whole book. Read this, and the world will never look quite the
same….
That morning, Watson and
Crick knew, although still in mind only, the entire structure: it had emerged
from the shadow of billions of years, absolute and simple, and was seen and
understood for the first time. Twenty angstrom units in diameter, seventy
billionths of an inch. Two chains twining coaxially…one up the other down, a
complete turn of the screw in 34 angstroms. The bases flat in their pairs in
the middle… a tenth of a revolution separating a pair from the one above or
below…one groove up the outside narrow, the other wide. A melody for the eye of
the intellect, with not a note wasted.
Horace Judson, The Eighth Day of Creation
Few things
could better express this tendency of jadedness toward the natural world than
how people regard DNA…and the entire subject of genetic inheritance.
Most
people are at least vaguely aware of what DNA is; any high school student who
has taken Biology 1A knows the gist
of its story. College students learn a somewhat deeper account, still very much
abbreviated. As for the entirety of the famed double helix’s astoundingly
elaborate narrative: among geneticists and molecular biologists (even including
educators in those fields), probably only a few are intimate with their area of
interest down to its finest minutiae. Meanwhile, a multitude of able
researchers resolutely work toward a goal of piecing together the final details
and filling in a few gaps.
Less than fifty years passed between the discovery
of DNA and completion of the Human Genome Project—largest collaborative
biological study in history. This colossal undertaking, bearing so much
promise, fell short of generating the world-wide enthusiasm resulting from
DNA’s discovery, despite plenty of media hoopla. Yes, times have changed, but
it leaves me cold whenever I encounter this strange, distinctly blasé attitude
(conveyed in speech or print) when the subject of “the miracle molecule” comes
up. And what this has to say about our conception of life, our collective lack
of imagination. No doubt this is partly the result of a shared cultural ennui
together with DNA’s profound—even alien—nature. Some people profess to believe
it is “just a chemical,”[1]
just another molecule, albeit a very
large one with some singular characteristics. Although DNA actually is just a chemical, nothing else is even
remotely in its class. And not just in the realm of chemistry: nothing at all. DNA is absolutely beyond
compare.
A
quick review is in order. Prepare to be astonished.
Deoxyribonucleic
acid, perhaps nature’s greatest innovation, is truly ancient. While almost
universally assumed to have arisen from simpler precursors, DNA has likely
changed hardly at all since life’s earliest days, so impeccably is it suited
for its all-important role. Earth’s surface has been repeatedly transfigured,
continents have come and gone, while this strange substance has persevered.
Nothing on Earth has remained unaltered for anywhere near as long. Every
individual molecule is uniquely different but identical forms of DNA reside
inside every cell of all known organisms, with few exceptions.[2]
Each strand has ties with the original in one unbroken hereditary chain. Though
seldom acknowledged, DNA’s antiquity and continuity are statements of tremendous import that color life’s entire
story.
The
molecule is shaped like a continually twisting ladder composed of two complementary strands. Both strands are
uninterrupted chains of modular subunits known as nucleotides, each of
which consists of a linked phosphate
(PO₄) and ribose
(a sugar, C₅H₁₀O) attached to another
component called a base. Every
nucleotide’s phosphate–ribose components form unvarying, identical subunits
joined end-to-end to fashion the molecule’s two backbones (the ladder’s upright
members). The base components, however, come in four varieties. Small, fairly
simple molecules, they line each nucleotide chain in a variable sequence. The
bases lie between the backbones, one from each side joined in the center by hydrogen
bonds,[3]
forming base pairs. In the ladder
analogy, these pairings represent the rungs and their shapes and arrangement
impart DNA’s twining configuration. Of critical importance: of the four bases
(their chemical names by custom abbreviated T, A, C, and G), T can bind only with A, C only with G.
These
bases, each with unique identities, comprise a four-letter genetic “alphabet”
from which the genetic code is
derived. (Genes are sequences of
these “letters”[4]
that are transcribed into coded instructions used to assemble ornately structured
proteins—an exceptionally important
class of molecules which, among their many roles, act as machines that perform
a multitude of vital tasks.[5])
The two strands are complementary; during mitosis (the process of cellular
division) they are physically separated and each half is used as a template to
make a replica of the other.
Thus,
once reconstructed, there are two copies (both identical to the original) and
each daughter cell receives one. This is how genetic information is passed on;
each cell bears all the information needed to construct an entire organism but
most of that information is either never used or is “switched off” when not
needed. In eukaryotes—life forms whose cells possess a membrane-bound nucleus
where all genetic material resides—DNA is bundled into a number of discrete,
paired packages called chromosomes. But in the unicellular prokaryotes
(organisms such as bacteria) just one or two circular chromosomes float freely through each individual’s watery
interior.
Human cells each have 23 pairs of chromosomes
(one set from both parents) for a total
of 46; the different pairs vary considerably in size depending on the
quantities of DNA they contain. Also: different types of organisms have
different numbers of chromosomes—a figure that can vary a great deal even in
similar groups, with no obvious pattern. (For instance, the number in a single
genus of ant, Myrmecia, ranges
between two and 84 depending on the species.)
Consider
these curious facts: In humans, if all the DNA contained in just one cell’s 46
chromosomes (by some estimates comprising around 200 billion atoms[6])
were stretched out and laid end-to-end to form a single strand, though only ten
atoms wide it would be almost six feet long. In our bodies, each cell’s set of
chromosomes contains an estimated 3 billion DNA nucleotide “letters”—all this
compactly stored in its nucleus. Our bodies contain around 30 trillion cells, a
figure that amounts to roughly 450 times Earth’s current human population.[7]
Thus: if all one’s personal DNA were drawn out and laid end-to-end it would
wrap around the equator [Drum roll,
please!] well over one…million…times. Ladies and gentlemen! Pause for a
moment and try to consider what these weird and wonderful things might signify.
Keep in mind: all that DNA fits inside your
body. It is inside you right now.
Normally,
chromosomes are loose in the nucleus in the form of slender threads made up of
the actual DNA molecules wrapped around spool-like structures called histones. These bundles are coiled
tightly into chromatin fibers which,
for the most part, float freely but are attached at many points to the nuclear
membrane’s inner surface. However, prior
to replication they have to be isolated and further compacted. No simple
matter, this is accomplished with the aid of an army of protein helper molecules. (Amazingly, there are
some 4000 specific types of these assistants.) The cobweb-like array is
detached from the nuclear membrane and the chromosomes twisted into tight
coils. These twist into tight coils that coil yet again, resulting in a dense
clump of genetic material. After replication and division, the process is
reversed and the new chromosomes are unwound. But, before the chromosomes
briefly take on their so-called “condensed” form (the plump “X” shape people are most
familiar with) they have to be replicated.
The
duplication process is staggering in its complexity and exacting coordination.
Prior to mitosis the chromatin fibers are unwound, making them accessible to
swarms of replicating enzymes. (Enzymes are special protein molecules
that assist with reactions; more about them shortly.) There are numerous replication sites on each chromosome and
the DNA is duplicated in short stretches that are detached and later rejoined. Replisomes,
complexes of various protein machines involved with the duplication of the two
strands after separation, work in paired teams. Around 100 pairs seize specific
places on their chromosome and begin working in opposite directions, churning
out new strands at the rate of 50 nucleotides per second. Each of the
chromosomes are duplicated simultaneously; with thousands of replisomes
operating throughout the nucleus, all the cell’s DNA can be replicated in about
an hour.
A
family of more than 30 types of enzymes is involved: helicases separate the two
strands; DNA polymerases gather free-ranging nucleotides and place them in
position. Topoisomerases “relax” the
tightly coiled DNA and one type, gyrase,
keeps the twisting strands from becoming hopelessly tangled by temporarily
breaking them and allowing the kinks to unwind before rejoining them. While the
two halves are divided they are highly reactive; to prevent them from being
chemically attacked or re-attaching prematurely, single-strand binding proteins are called up to temporarily cap the
exposed nucleotides. Ring-shaped clamp
proteins form a sliding clamp around the DNA near the point where the two
strands are separated to help the polymerase maintain firm contact with the
section being replicated.
This
is a mere sample of the players involved. As remarkable as it might seem, the
entire, fantastically intricate extravaganza is understood in precise detail.
And those details, in both number and kind, are almost beyond belief. (This
limited description be-lies the true state of affairs.) What is not known, though, is how the whole
performance is coordinated so seamlessly, how the strict sequences are timed
and reaction rates controlled. And just how seldom things go wrong (especially
compared to any human endeavor). A single mistake—just one—can be fatal for any
cell. Or, if the error turns up in an egg or sperm cell, fatal to the
organism’s offspring. That one slip-up could result in a defective gene, which
might lead to the imprecise formation of a single type of protein, which in
turn could result in something like type 1 diabetes or sickle cell anemia.
So:
accuracy in the entire process is crucial. Suites of repair enzymes proofread the duplicated strands and mend damaged or
incorrect sections. Robert Wesson writes:
“One
set…monitors that the right amino acid is put in place; another set checks that
the newly forming DNA corresponds to its template and cuts out and replaces
defective sections; a third confirms the finished product,” in the case of E. coli making less than one error per
billion letters. And just for a reminder that these efficient workers are
complex machines and not little toy-molecules: one of the repair enzymes,
composed of some thousands of atoms, is named phosphatidylinositol 3-kinase-related
kinase.
Among
its many astonishing properties are DNA’s surprising durability and chemical
stability. Still, it is constantly being damaged due to various kinds of
physical impairment, from oxidation by free
radicals (highly reactive molecules and ions) or, in skin cells, exposure
to ultraviolet light or X-rays. But thanks to teams
of fix-it enzymes, the DNA of each individual cell can undergo repair from
10,000 to one million times per day, most
of it successfully. Close to 170
specific varieties of enzymes are involved with different aspects of DNA repair
(including the much different problems associated with sigle-strand repair as
opposed to mending a double-strand break). The entire process is now recognized
as being absolutely essential for the survival of all organisms. According to
recent estimates, without these proofreading and repair systems, roughly 1% of
bases would fail to be copied correctly—a quick and certain route to
extinction.
Not
bad…no, not too bad for something that is “just a chemical.” Bearing in mind
that DNA is “only” a molecule,
consider once more its bewildering sophistication: a lifeless aggregation of
atoms that orders the construction of virtual armies of assistants; these
helpers then unwind it, take it apart, and faithfully reattach these fragments
after making sure they have been copied accurately. This, a consequence of the
DNA having supplied another suite of elaborate protein machines with blueprints
for the assembly of all those helpers (together with furnishing
instructions for the fabrication of
the machines that built the machines.)
In
addition, DNA fixes its own damaged parts and mistakes made while being rep…li…ca…ted. For some reason,
incomprehensible to me, most people do not seem to think that self-assisted
self-replication is too tall of an order for a mindless molecule.
And as for
DNA’s role in the process of genetic inheritance: that equally remarkable saga
will be delved into later. Suffice it to say, for now, that the tale shares the
same qualities of neat efficiency and dazzling intricacy. Another extensive
team of molecular players in backing roles help bring forth all its enormous
potential.
Never
overlook the fact that DNA is not only entirely passive but utterly useless
without the help of its legion of confederates, each of them being equally essential.
The miracle molecule is plainly not alive in any accepted usage of the word.
But how can we continue to ignore the obvious? That in some sense DNA (along
with the entire system-cum-process involving a host of assistants) is animated
by the same quality—whatever it might be—that separates living from nonliving?
At what point do these far-fetched molecular associations and interactions earn
new biological status? Or, from a non-scientific point of view, at least a
different sort of emotional response?
Viewing these matters through the lens of
Natural Design provides a standpoint from which such wonders meld perfectly
with the greater picture of what life is
capable of. The double helix could be considered the ultimate expression of
nature’s creativity. It did not simply “happen”—it was a necessity invented by nature to fill an indispensable
role. The late Bill Gates wrote, “DNA is like a computer program but far, far
more advanced than any software ever created.” As a chemical solution to the
problems of reproduction and inheritence, it has functioned flawlessly for
going on four billion years. True to its paradoxical nature, DNA’s unwavering
stability makes life possible while
an innate fluidity makes it possible for living things to evolve. And life’s
built-in knack for changing through time in beneficial ways is central to its
success.
©Tim Forsell draft
27 Feb 2017
[1] Wade, N. (1995) “Method & Madness; Double Helixes,
Chickens and Eggs,” New York Times
Magazine. “An ark’s worth of species flower and fade at
each tick of the geological clock. Only DNA endures. This thoroughly depressing
view values only survival, which the DNA is not in a position to appreciate
anyway, being just a chemical.” (Wade, it should be noted, is explicitly
writing with reference to Richard Dawkins’ “selfish gene” theory.)
[2] One instance is vertebrate organisms’ red blood cells,
which have relinquished their DNA (and the cell’s entire nucleus) in the
interest of smallness—the better to navigate through minute capillaries and
carry more oxygen.
[3] Unlike covalent
bonds, wherein atoms “share” electrons, hydrogen
bonds are much weaker. They form between separate molecules when a weakly
positive hydrogen in one molecule is attracted to a slightly negative atom in
the other. Hydrogen bonds are of great importance in nature (accounting for the
fluid properties of water, for instance). The hydrogen bonds between the
nucleotides, it should be noted, are a most opportune balance between the
strength needed to maintain the molecule’s durability and what is necessary for
the two strands to be easily separated.
[4] To be clear: these “letters” form the basis of a
language analogy and are unrelated to the bases’ single-letter abbreviations.
[5] Proteins are a class of organic (carbon bearing) molecules. There are around a million
known varieties. Unlike inorganic
polymers—chains of repeated elements or monomers—proteins
are made up of highly specified sequences of modular building blocks called amino acids. Chains of amino acids are
joined together to form polypeptides,
which are then further processed to
create the proteins. These act singly or in combination, making up the cell’s
working parts.
[6] Note throughout this work that most of these
impressive “facts” are, in actuality, akin to estimates or “educated guesses.”
As is customary, they were conveyed without any qualification as to their range
of accuracy. Some could easily be off by orders of magnitude.
[7] Estimates of extremely large numbers (some of them apparently
little more than wild guesses) may be off by several orders of magnitude.
Whatever the figure: it is obviously somewhat arbitrary, particularly when
dependent on a number of factors.
