Sunday, May 28, 2017

The God Molecule

I am a convinced evolutionist. Having worked in a biotech firm that made genetic analysis equipment and reagents, and so having learned a bit about biology, I can see the relationships among all life on this planet through our shared inheritance of the DNA-RNA-protein coding system. Everything on this planet that we think of as being alive—from bacteria to bats to banyan trees—uses this system. And every species, genus, family, order, class, and on upward through the traditional biological classifications attributed to Carl Linnaeus in the 18th century can be measured and compared by the number of shared genes and genetic mutations the representative organisms possess within this coding system.1

It’s not that every organism has a “DNA-like” system, allowing for some mechanical or chemical variations. No, they all—from slime molds to sea urchins to sparrows—use the same DNA system, intact and whole. That system has four bases—adenosine (A), cytosine (C), guanine (G), and thymine (T)—which are always paired A to T and C to G. It arranges these four bases, which are variously purines or pyrimidines, in a three-base “reading frame” yielding sixty-four possible code combinations, called “codons.” It uses these combinations to call up just twenty amino acids from among the 200 or more amino acids that exist in nature.2

There are minor variations within the system itself. For example, DNA differs from RNA in that the second carbon atom in the sugar ring of each base has an attached hydrogen atom (H) rather than the hydroxyl group (OH) found in RNA—and thus DNA is the “deoxy” ribose nucleic acid. And the RNA strand itself substitutes the base uracil (U) for thymine (T) in transcribing the coding sequence. But those are about the only differences—and they are used in all branches of life.

All organisms use the same DNA start codon ATG—the only codon calling for just one amino acid, methionine—as the beginning of any protein-coding gene and as the start of the messenger RNA strand (where it’s written AUG) that will translate the gene into a protein. So all protein strings start with methionine. And all organisms use one of the three DNA stop codons TAG, TAA, or TGA (in RNA as UAG, UAA, or UGA)—and none of these sequences codes for any amino acid—to end the gene and its corresponding messenger RNA strand.

Nowhere on Earth do we find organisms that use a different coding system; or use different bases from among the eight possible purines and pyrimidines found in nature; or employ a four- or five-base reading frame for more possible combinations, or a two-base frame for more compact and efficient coding; or call on a different set of amino acids to create new and exotic proteins. Some of the mechanisms that support the system are different. For example, single-celled prokaryotes, which have their DNA scattered throughout the cell body (rather than contained within a nucleus, like the multi-celled eukaryotes), use a different ribosome to translate the messenger RNA strand into a protein string. This is one of the reasons you can take an antibiotic to kill the bacteria in your body without harming your own cells: the medicine attacks the bacteria’s protein coding mechanism, and yours is different from that of the bug that’s infecting you.

As a mechanism for evolution, the DNA-RNA-protein coding system is superb. The DNA molecule is fragile, susceptible to environmental abuse through radiation and chemical assaults. But the system itself, with sixty-four bases calling twenty amino acids, has a lot of redundancy. You can change or knock out the third base in the reading frame’s codon—sometimes even the second base—and you still have a good chance of calling the appropriate amino acid.3 And large complex proteins often have parts of their molecular structure that can be modified or removed without changing their essential function. If some smart person were trying to design a chemical system that allowed for environmental change, but not too much and not too fast, the DNA molecule would be it.

And one of the great biological and geological understandings of the past hundred years or so is that the Earth’s environment is constantly changing, and that species must continuously change with it or else they would die out quickly. Our Sun goes through millennial and epochal cycles of warming and cooling, the continents drift over the ages on tectonic plates, mountains rise and erode away, streams meander and shift, lakes form and evaporate. An animal or plant species that could not change its form or function in some degree, large or small, over the generations would not survive in this changing landscape.

So the old Platonic idea, preserved in Genesis, is pure intellectual fantasy. Plato held that, while horses in the field may come in many varieties, different sizes and colors, shapes and strengths, there exists somewhere an ideal form—the Horse, perfected in the mind of God. This gives rise to the notion that a species, like Equus ferus caballus or Homo sapiens has some mystical, “pure” essence. But each variety of horse, as well as those of zebras and donkeys, were all adapted through a haphazard blending of mutational changes to fit its particular niche in an environment that was basically solid, level ground suitable for running over and covered with grass that was good to eat. If it had benefited the horse family to have toes like wolves or lions—or like their ancestor, the multi-toed Eohippus—instead of hooves, then we would now have horses with toes. If an early horse family and its line of ancestors going back millions of generations to some Theropoda dinosaur had evolved the metabolism to fill a niche that profited from eating grubs and worms, then we might now have horses with beaks.

But there’s paradox in all this. While the DNA-RNA-protein coding system is admirably suited to evolve the organism it creates and fit that species into its current environment, the system itself shows no hint of its own evolution.4 Again, the supporting mechanisms may have evolved, like the various forms of ribosomes. For example, the single-cell prokaryotes have DNA chromosomes that are looped in a double-stranded structure, called a “plasmid,” that floats inside their cell bodies, while the multi-cell eukaryotes have chromosomes that are tightly coiled, wrapped around knobs of protein called histones, and segregated inside the cell’s nucleus. In either case—from Salmonella typhi to salmon—it’s the same DNA, transcribing its code onto messenger RNA, which some form of ribosome then translates into a protein.

It is possible that the Earth originally spawned multiple coding systems. DNA-RNA-protein might have been in competition with other molecular forms and chemistries.5 For example, within the domain of our current carbon-based organic chemistry, early life forms might have employed more bases, larger reading frames, and more amino acids from which to choose. The evolutionary development of something as fundamental as a molecular coding system would have taken place so early in the start of life on this planet that other competing forms might have died off before the crust quite cooled. And these complex chemistries, without the skins, shells, and scales of organic bodies to protect them, would have vanished without a trace in the turbulent environment of early Earth. But surely somewhere, hidden among the lichens and fungi, the bacteria and the molds, shouldn’t we have found an example of some poor, under-developed organism that preserved at least one of these alternate coding systems? No, nowhere. Not in the strange tube worms and sea spiders clinging to a volcanic vent in the deep ocean a hundred miles from their nearest organic neighbors. Not in Antarctic lakes buried under miles of ice for millions of years. The entire living world is created from the same DNA-RNA-protein coding system that gives us mangos, manatees, and human beings.

Which raises the tantalizing prospect that this coding system did not evolve here in the first place. Maybe it was seeded when a carbon-based astronaut from a distant star, who was visiting Earth soon after the crust hardened and the oceans formed, dropped a glove with a bit of his/her/its cellular chemistry attached. Maybe a spore of some alien bacteria blew into the solar system on a grain of dust from some other star system.

And there are people who can accept that organisms may evolve through changes in their DNA but who doubt that the basic chemistry—those ribose rings and phosphate bonds, the structures of purines and pyrimidines, and all the rest—could have come together in the first place to record molecular traces. Not here, and maybe not anywhere in the universe. And even if those first long-chain molecules could arise here or elsewhere, why would they? What would they be preserving for posterity, other than their own coding? And then, why would they put together A and T, C and G, in preference to any other combination? For, after all, molecules at that level might form spontaneously, but they wouldn’t create anything. Eventually, they would break apart under the stress of some other chemical reaction. Bare molecules have no reason to preserve one sequence as more successful in their environment than any other.

Although I am not a deist and have no belief in a supreme being, it is possible that the DNA-RNA-protein coding system was designed for the purpose that it so admirably fulfills. DNA and RNA are not even that hard to make. At the biotech company, we had factory that manufactured the ribose rings with their attached bases and their phosphate-bonding tails. We synthesized long chains of single-stranded DNA as primers designed to anneal to the sequences in wild DNA, copy them, and then reproduce to amplify them, in the process known as “polymerase chain reaction.” This is the basis of most techniques of genetic analysis and sequencing. We now know how to knit those synthetic strands of DNA into artificial chromosomes, wrap them in a coat of proteins and lipids similar to a cell membrane, give them a basic metabolism, and nurture them in the laboratory as a primitive cell.6

If human beings can master—or at least start using—this technology a mere sixty years after we first defined the DNA molecule, then a more advanced civilization on a planet around one of the billion stars in the Milky Way, or in one of the trillion other galaxies in our universe, might have become very good at this kind of synthetic creation. Perhaps this forefather civilization was carbon- and DNA-based itself, and they metaphorically plucked a rib from their side and turned it into the seeds that became all life on Earth and perhaps on other planets, here and around other stars. In that case, they might know the secret of how the first DNA coding system itself evolved. Or perhaps these scientists or missionaries—or gods—evolved in some other form and merely thought up the DNA-RNA-protein coding system as a good way for creating that temporary reversal of entropy we call life.

And maybe—I’m just freewheeling here—there really is a Supreme Being, an All Soul, a Divine Spark, Which/Who touched the Earth’s chemistry with its all-seeing inspiration and foreknowledge, and thereby designed a molecular system that would transform a barren planet into one teeming with chemical energy, adaptability, and eventually with thought itself.

1. See also DNA is Everywhere from September 5, 2010.

2. Two additional amino acids in common use are added to some proteins by enzymatic action after the messenger RNA sequence has been translated into the polypeptide chain.

3. See, for example, this chart of the genetic code from a biology course at Kenyon College.

4. Well, one hint. The RNA molecule is always single stranded, and that OH group on the second carbon in each base keeps the long-chain molecule from coiling around itself. DNA is always double stranded, and that missing oxygen lets it form the iconic helix shape. So the RNA form is simpler, straighter, more exposed to chemical damage, and perhaps more primitive. This suggests to some biologists that, as a record-keeping molecular system, RNA may have come first and then DNA, with its tighter, more complex, more robust structure, may have evolved from RNA. But we find no living organisms that use only RNA not in combination with DNA. However, some viruses, called “retroviruses,” have RNA-only coding and use a reverse transcriptase to make DNA copies of their code once they invade a host cell.

5. For example, it’s possible to imagine a silicon-based life form, with silicon taking the place of carbon in its DNA-surrogate’s ribose rings, purines, and pyrimidines, and with arsenic taking the place of phosphorus in the phosphate bonds that provide cellular energy and knit together those ribose rings into the DNA structure. Such a system would have heavier molecules, because the component atoms have a higher atomic weight, and the molecular bonds would be weaker, because the electrons holding the atoms together would be traded among shells farther out from their atomic nuclei. However, such heavy, fragile molecules would be at a disadvantage in competition with a lighter, stronger DNA molecule.

6. See, for example, “ ‘Minimal’ cell raises stakes in race to harness synthetic life” in Nature News, March 16, 2014.

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