II. The Miracle Molecule
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 personify this tendency of jadedness toward the natural world better 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 called nucleotides, each consisting of a phosphate and a ribose sugar
joined to another part known as a base.
The nucleotides’ identical phosphate-ribose components are small organic
molecules joined end-to-end to form the molecule’s two backbones (the ladder’s
upright members). The base components, which occur in four varieties, are also
small molecules that line each chain like dewdrops on a spider’s web. Between
the backbones, representing a ladder’s rungs, are nucleotide base “pairs”—one
from each side joined by hydrogen bonds—and
their arrangement imparts DNA’s twining configuration.[3]
And this critically important fact: of the four bases (their chemical names
customarily 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 translated into coded instructions for assembling 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 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
eighty-four 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. (If that strand were enlarged to
the thickness of one’s little finger, it would stretch from San Francisco to
Paris.) In our bodies, each cell’s set of chromosomes contains an estimated 3
billion DNA nucleotide “letters”—all this compactly stored in its nucleus.
(About 200 average-sized human cells would fit in the period at the end of this
sentence but the DNA they contained, stretched out, would be 400 yards long.)
Our bodies contain around 60 trillion cells—a figure that amounts to roughly
900 times Earth’s current human population.
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 two…million…times. 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…is inside you 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
assistance of an army of protein helper
molecules. (Amazingly, there are some 4000 specific types of these.) 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 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 later.) 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 are separating 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’re 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 just a
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 belies the true state of affairs.) What’s not known, though, is how the whole performance is coordinated so
seamlessly, the strict sequences timed and reaction rates controlled, and how
seldom things go wrong (especially when compared to any human endeavor). A
single mistake—just one—can be fatal
for the cell. Or, if the error turns up in an egg or sperm cell, fatal to the
organism’s offspring; that one slip could result in a defective gene, which
might lead to the irregular 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. However, thanks to fix-it enzymes like photolyase, an individual cell’s DNA undergoes repair ten thousand
times per day, most of it successfully. Close to 170 specific varieties of
enzymes are involved with DNA repair.
Not bad…no,
not too bad for something that’s “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 those helpers—and furnished
instructions for their fabrication as
well.)
In addition,
DNA fixes its own damaged parts and the mistakes made while being rep…li…ca…ted. For some reason,
incomprehensible to me, most people don’t seem to think that self-assisted
self-replication is too tall of an order for a mindless molecule.
DNA is clearly
not alive in any accepted usage of the word. But how can we ignore the obvious:
that, on some level…in some sense, DNA 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 DNA
through the lens of Natural Design provides a standpoint from which its wonders
meld perfectly with the greater picture of what life is capable of.
©2016 by Tim Forsell draft
28 Jan 2016
[1] Nicholas Wade, in “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] The chemical
bond between the nucleotides, it should be noted, is 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 molecules known as biopolymers. Unlike inorganic polymers, with their long chains of
repeated elements (monomers), they
are made up of highly specified sequences of building blocks in the form of
modular elements called amino acids.
Proteins act singly or in combination to make up the cell’s working parts. At
present, there are around a million known varieties.
[6] Note throughout this work that most of these
impressive “facts” are, in actuality, akin to estimates or “educated guesses.”
As is so common, they were conveyed without any qualification as to their range
of accuracy. Some could easily be off by orders of magnitude.
No comments:
Post a Comment