Arrival of the Fittest: Solving Evolution's Greatest Puzzle (26 page)

Genotype networks are yet another example of the pervasive self-organization we first encountered in chapter 2—the same phenomenon that pervades both the living and nonliving worlds, from the formation of galaxies to the assembly of membranes. But they are a peculiar example of self-organization. Unlike galaxies, which self-assemble through the gravitational attraction of cosmic matter, or biological membranes, which self-organize through the love-hate relationship of lipid molecules with water, genotype networks do not emerge over time. They exist in the timeless eternal realm of nature’s libraries. But they certainly have a form of organization—so complex that we are just beginning to understand it—and this organization arises all by itself. And as with galaxies and membranes, the principle behind their self-organization is simple: Life is robust. This robustness is both necessary for genotype networks—otherwise synonymous texts would be isolated from one another—and it is sufficient.
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Wherever metabolisms, proteins, and regulatory circuits are robust, genotype networks emerge.

Robustness is sufficient to create genotype networks, but genotype networks alone are not sufficient for evolution. The reason is that evolution must meet two demands, seemingly at odds with one another. It must be simultaneously conservative and progressive, like some aviation pioneer embarking on a transatlantic flight in the Wright brothers’ original flyer: Certain in the knowledge that he must invent a new design to complete the journey, he must also keep the old one in the air until he does. Nature must keep what works alive while exploring the new. Genotype networks are essential for exploration. But they aren’t made for conservation.

This bears emphasizing, because the exciting new discoveries about genotype networks can tempt us to forget the critical importance of natural selection. Conservation is the job of natural selection—evolution’s memory—and its power to conserve even tiny improvements, given enough time, is so great as to seem absurdly unbelievable. Literally so. In the
Origin
Charles Darwin
wrote about eyes, surely among the most spectacular innovations in life’s history, “To suppose that the eye with all its inimitable contrivances for adjusting the focus to different distances, for admitting different amounts of light, and for the correction of spherical and chromatic aberration, could have been formed by natural selection, seems, I freely confess, absurd in the highest degree.”
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When light passes through our eye, the lens projects a fantastically accurate, undistorted image of the outside world onto our light-sensing retina. To do so, it must
refract
light’s path, changing its direction at a precise angle.
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It’s not just the lens’s shifting shape that makes this possible, but also the less appreciated and peculiar lens material—an ancient innovation that required nothing but new regulation.

Shine a flashlight obliquely onto a body of water, and you will see that the light ray kinks at the surface. Dissolve sugar in the water, and the kink’s angle gets sharper—the more sugar you dissolve, the sharper it gets. (The food industry uses this principle to measure the amount of sugar in wine, soft drinks, and juices.) Our eyes refract light just like that, except that they use proteins instead of sugar. These proteins—crystallins—occur at very high concentrations in the lens, which allows the lens to refract light strongly.

Crystallins are so uncannily good at refracting light that it’s tempting to think that they were tailor-made for constructing lenses, and therefore rare. Not true. Many crystallins are metabolic enzymes, the very same enzymes that promote chemical reactions elsewhere in the body, albeit in smaller numbers. Different organisms use different enzymes as crystallins. What distinguishes them from other proteins is that they do not clump easily, not even when they are expressed at the extreme concentrations needed in the eye.
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Eyes build their lenses out of proteins like the one that detoxifies alcohol, just because they confer transparency—the same way you might use an old brick as a bookend simply because it happens to be heavy. Crystallins are also some of the sturdiest proteins around, so long-lived that the crystallins that make up the lens of the human eye last an entire lifetime, from birth to death.
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But sometimes they wear out and start to clump, making the lens milky white. When this happens a cataract has formed, with consequences both well known and disastrous: blindness.
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Though Darwin knew nothing of protein chemistry, he did suspect—and today we know—that the fancy eyes of vertebrates with their sophisticated lenses are the last in a long list of gradual improvements. Long before our ancestors started co-opting nonclumping metabolic proteins,
their
ancestors, like some worms and starfish, were using flat patches of light-sensitive cells that were at least good enough to find a shadow to cower in and hide from predators. After millions of years, these cells eventually congregated in shallow bowls,
eyecups
that can detect light’s direction better, which deepened into
pit eyes
that can detect it very well, and even further into
pinhole
cameras whose tiny openings can produce real images. From there it was one more step to lenses, transparent tissues of higher density that—thanks to crystallins—could focus light. Eventually these lenses became able to flex or move to create sharp images.

All these small, gradual improvements are worth preserving, and natural selection did. We know, because many animals still have them: eyecups in some flatworms, pit eyes in some snails, pinhole camera eyes in the nautilus—a relative of squids that builds many-chambered shells—and simple lenses in organisms as primitive as jellyfish.
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It’s a bit like the stunning grandeur of medieval cathedrals, with soaring spires, columns of heavy massive stones assembled with exquisite precision, and vaulted ceilings so high that our gaze gets lost in their semidarkness. The finished product—like the human eye—is literally incredible without the knowledge that it was built one brick at a time.

The same is true for all molecular innovations. The amino acid text of the Arctic cod’s antifreeze proteins didn’t originate in a single step, like Athena springing from the brow of Zeus. But every single letter of an ancestor’s amino acid text that changed in the right direction, lowering a body fluid’s freezing point by as little as a tenth of a degree, could expand its descendants’ habitat by miles. A greater range means a larger and more varied food supply. It means a change well worth preserving, and a long sequence of such tiny changes can expand life’s frigid frontier by long distances. Genotype networks are crucial to find each such change, and natural selection is crucial to preserve it.

Better variants that improve an organism incrementally are important for innovation, but they are not the only kind of change that DNA experiences. Many mutations neither harm nor help when they first arise. Such
neutral
changes are a consequence of life’s robustness and the disorder it allows.

That neutral changes could matter for innovation—and why—was not always clear. In fact, the relationship between natural selection and neutral change was central to a historical controversy that tore at the fabric of Darwinism in the last third of the twentieth century. The revolution in molecular biology, then well under way, had revealed that populations of wild organisms, from mammals to fruit flies and down to bacteria, harbored astonishing amounts of genetic variation: The DNA of thousands of genes in members of the same species varied in its letter sequence. Most scientists, good Darwinians as they were, believed that the fate of most of these variants was determined by natural selection—variants that appeared frequently must improve survival or reproduction.

But these selectionists were opposed by a vocal minority, the neutralists, who argued that most of these variants make no difference to the organism and are invisible to selection. At least when they first appear, they are neutral. In the eyes of some, like the paleontologist Stephen Jay Gould, the very existence of neutral change compromised the importance of natural selection in evolutionary innovation.
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The history of science and technology offers loose analogies for how neutral changes—dormant discoveries—can become valuable for future innovations. Number theory provides one such analogy. It is a branch of mathematics about which the American mathematician Leonard Dickson reportedly said, “Thank God that number theory is unsullied by any application.”
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This was as true in 1919 as it had been since Euclid, but within decades unrelated developments—digital computers and networked communication between them—placed the theorems of number theory at center stage of the Internet economy, where they ensure the secure communications that make e-commerce and online banking possible. In a similar vein, the German physicist Heinrich Hertz, whose experiments validated the electromagnetic theory of James Clerk Maxwell, saw no practical purpose to his discovery. He reportedly said that it was “of no use whatever” and “just an experiment that proves Maestro Maxwell was right.” Less than forty years later, his discoveries led to the first commercially licensed radio station in the world—KDKA in Pittsburgh, which still broadcasts on the frequency band of 1020 kilohertz.
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But back to biology, where the neutralists’ most outspoken proponent was the Japanese scientist Motoo Kimura, who had developed a sophisticated and successful mathematical theory to explain the evolutionary fate of such neutral mutations. Kimura asserted that
most
genetic variation seen in nature is neutral. The genomic era has taught us that he was wrong on that count—neutral variants are no more frequent than those providing an advantage. However, his hunch of neutral change’s being important was dead on, though it took another few decades to understand why.

One reason is that neutral change is critical for navigating genotype networks. Neutral change provides the browsers of nature’s libraries with a safe path to innovations through treacherous territory of meaningless texts. Without genotype networks and the neutral changes they allow, the exploration of nature’s libraries would be just about impossible.

Another reason is that a change that is neutral when it first appears doesn’t have to stay that way. Once-neutral changes can turn into essential parts of innovations—like the theorems of number theory. And once they do, natural selection can preserve them. Which means that both selectionists and neutralists had a point, because both kinds of changes are essential in evolution. After neutral changes have paved the way to an innovation, selection preserves those neutral changes that contributed to the innovation.

A single example from a well-studied RNA enzyme known as the hammerhead ribozyme can illustrate to what extent neutrality and genotype networks can accelerate evolution’s search for innovations. The job of this particular RNA enzyme is to cleave RNA at a particular point along its nucleotide strand. The shape of the ribozyme, named for its apparent resemblance to the hammerhead shark, is what allows it to perform this job—adequately but not necessarily optimally. Somewhere out in the vast library of all RNA molecules might be new shapes, new phenotypes that would endow the ribozyme with sharper blades.

If no genotype networks existed, then a crowd of readers in the RNA library—an evolving RNA population—would have to congregate around the forty-three-letter-long text that encodes the RNA, and could only explore the shapes that are one letter change away. This particular RNA enzyme happens to have 129 neighbors, and because we can compute their shapes, we can determine that there are forty-six new shapes in this neighborhood.
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That’s the number of shapes evolution can explore without genotype networks.