Life's Ratchet: How Molecular Machines Extract Order from Chaos (39 page)

The fossil ancestors of our molecular machines are, for the most part, gone forever. Proteins do not keep for over three billion years, and bacteria with primitive machinery would have been eaten a long time ago. Even the so-called archaea microorganism, which have been found to be significantly different from bacteria, are not really archaic. In some sense, bacteria and archaea are more evolved than we are. After all, they had a lot more time, and they reproduced much faster. With this in mind, is there
anything
that can be done to determine how molecular machines may have evolved?

Trying to figure out the exact evolutionary steps leading to the ribosome or a kinesin molecular motor is like trying to solve a crime hundreds of years after it happened. Who was Jack the Ripper? It is impossible to tell. The trail has gone cold. Yet, using the few reports and other scant evidence
that remains, we can make some plausible arguments about what kind of person he may have been. In much the same way, when it comes to the evolution of molecular machines, we have to look at the few remaining clues and try to come up with a plausible story. In this case,
plausible
means that the story matches the evidence and is in accordance with known physics and chemistry. Once a plausible story has been hypothesized, parts of it can be tested in the laboratory. If it passes these tests as well, we end up with a
likely
story, but we will never get a proven story. Jack will remain at large.

An instructive example is the evolution of the ribosome. In
Chapter 7
, I suggested that RNA is believed to be a more ancient molecule than either DNA or proteins. In the chicken-and-egg problem of what came first—DNA, which encodes protein, or proteins, which are needed to read the DNA—the answer is clearly neither. RNA contains information and can catalyze reactions. It is a kind of egg on feet, which can lay its own eggs. No chicken needed.

RNA’s ability to catalyze reactions is a fairly recent discovery. In 1982, Tom Cech and coworkers at the University of Colorado–Boulder discovered that a certain RNA strand in a bacterium was able to splice parts of itself and reconnect the RNA strand, without any protein-based enzymes. This was the first indication that RNA could act as an enzyme. It took another ten years before Harry Noller and his group at the University of California– Santa Cruz demonstrated that the RNA in the ribosome also has catalytic properties. Over the years, it became clearer that
all
the hard work in the ribosome is done by RNA. When researchers removed the protein components, the RNA was still able to process messenger RNA and produce an amino acid chain, although at some loss to efficiency and fidelity.

The finding that the ribosome needed its RNA, but not its proteins, suggested that catalytic RNA may have been the basic constituent of early life. In a paper in 2010, researchers from the Weizman Institute of Science in Rehovot, Israel, and the European Molecular Biology Laboratory in Heidelberg, Germany, suggested that the RNA pocket where the amino acid chain is assembled is universal in all ribosomes and may constitute the original ribosome precursor. If RNA really was first, and it could catalyze its own evolution through splicing and reshaping, it may have eventually hit on a structure that could produce proteins. After that, proteins that
assisted the primitive organism by being better catalysts than the RNA could have formed. This first protein-producing RNA may not have been able to create well-controlled protein products, but less control would have also led to more mutations and possibly faster evolution. Eventually, the combined forces of RNA and proteins invented DNA, and the modern cell was on its way. It is a likely story.

Another way to consider the evolution of molecular machines is to look at family relationships. In the previous chapter, we mentioned that kinesin and myosin share many similarities in their motor domain. This suggests that they may have evolved from a common ancestral protein. Myosin and kinesin share certain loops in their switch domains, which are associated with shape changes upon binding of ATP. Intriguingly, they also share these structures with so-called G proteins, which are not machines, but molecular switches. Molecular switches communicate chemical signals from the outside of the cell to the inside. In
Chapter 6
, we speculated that molecular motors may have evolved from enzymes that could change their shape when they bound a control molecule. This allosteric effect is what makes molecular switches work.

The details of how G proteins connect to kinesin and myosin is lost in the fog of billions of years of evolution. Nevertheless, that motor proteins would have evolved from molecular switches is very plausible, and the relationship with G proteins confirms this idea. The relationship between kinesin, myosin, and G proteins shows that in evolution, similar parts in different molecules can often serve different purposes. The evolution of a sophisticated machine like kinesin does not require that each part be invented from scratch or that all parts come into existence simultaneously. When it comes to evolution, almost anything goes.

Let us imagine two proteins A and B, encoded by certain genes in our DNA. Proteins A and B perform different functions. What if part of protein B could help make protein A work better, or what if the combination of parts from A and B were to create a new protein with a completely new function? No problem. Sometimes, whole protein sequences are translocated in our genome, either through copying errors or by viruses. This can lead to the combination of different proteins and the creation of an entirely new line of molecular machines. An example is the nylon-eating enzyme of
Flavobacterium
.

Ever since kinesin and myosin came into existence eons ago, they have evolved into many different forms, forming large superfamilies. We have seen an example for such a family tree in
Chapter 7
. The same is true for almost any molecular machine. Every protein is part of a family of related proteins whose jobs are often quite different, but which are clearly descendants of a common ancestor. Evolution never ends; it is ongoing. Once evolution discovers a new trick, such as a walking molecular motor, it soon creates many variants, all fulfilling specialized functions.

A common objection of creationists is that some biological structures are “irreducibly complex.” What they mean is that a structure has many interdependent parts, so that if you remove just one, the whole thing could not work. For example, how could a car evolve? The engine could not evolve without already having a whole car in place. But the car could not evolve without an engine. All the parts of a car must be designed to fit together. No part can be left out. Thus, goes the argument, molecular machines must be
designed
, just as a car is designed. This is because (following their argument), a molecular machine is only functional when all the parts are in place. There can be no intermediate evolutionary steps. Every previous version of the molecular machine—without all the necessary parts in place—would have been utterly useless.

There are a number of problems with this superficially persuasive idea. First, as we have seen, structures are often put together from parts that previously served a completely different purpose. Take the car example. Clearly, different parts of the car can be developed independently of the whole car. An engine can drive a stationary machine. The Cardan shaft of today’s automobiles, as we saw in
Chapter 2
, was invented for a water pump. Pistons come from air pumps. Gears from watches. And so on. There are countless examples of such versatility in evolution. The bones in our middle ear evolved from a jaw bone of an ancestral amphibian. The evolution of motor proteins from molecular switches, like G protein, is another example.

The second problem with the irreducibility argument is that incomplete structures are not as useless as one might think. Take the eye. Is an eye without a lens really useless? It sure beats no eye at all. Almost all intermediate stages of eyes exist in nature, from mere light-sensitive spots of some microorganisms to the sophisticated eyes of mammals. The same
applies to motor proteins. We have seen that two-legged motor proteins can be processive. However, one-legged motor proteins can work as well, although with much less efficiency and highly reduced processivity, using a pure Brownian ratchet mechanism. Indeed, as we have mentioned, there are one-legged kinesins—although the jury is still out as to whether they can pair to form a two-legged kinesin. Nevertheless, at least theoretically, there is no physical reason why such a one-legged kinesin would not work. It may not be as good as kinesin-1, but it’s better than no kinesin at all.

Many biologists consider evolutionary changes of DNA the most important events in the history of life. One proponent of this view is evolutionary biologist Richard Dawkins, famous for his idea of the “selfish gene.” While there is, of course, much to be said in favor of this view, biologists often underestimate the role of physical law. The DNA-centered view therefore emphasizes chance over necessity. This has been exploited by creationists who like to abuse the concept of chance in evolution to claim that evolution is random and that randomness alone could not have created the complexity of life.

If evolution were truly random, the probability of creating just one functional protein would be astronomically small. Calculating such probabilities is a common parlor game among creationists. But these probabilities are irrelevant. Evolution is
not
random: It is the collaboration between a random process (mutation) and a nonrandom, necessary process (selection). It is the result of the balance of chance and necessity. This is not unusual—
all of nature is the result of this balance
. If not, nature would be either a featureless structure that is the same everywhere (if necessity wins) or a random “mush” with no structure at all (if chance wins). The exquisite order and the amazing variety we see in nature at every level—from galaxies to molecules—is the result of the fruitful interaction of chance and necessity. What is the probability of Earth or a pebble? It’s a meaningless question. Similarly, the question about the random assembly of a protein is also meaningless. Evolution is not random.

Another favorite question of creationists is “How did all the information get into DNA?” At first glance, questions about information in DNA seem legitimate. This is because the message in DNA has meaning. It encodes the structure of a protein or regulates the development of an organism. But is meaning the same as information? Information is measurable; meaning
is not. Creationists conflate these two terms to suit their own ends. In information theory, a message has more information the more random it is. As we mentioned before, a perfectly ordered message contains little information. AAAAAAA contains no information, while ACTTGATTC contains information. But does ACTTGATTC have meaning?

The whole idea of DNA containing information is, in my opinion, one of the main culprits in maintaining the myth of creationism and intelligent design. First of all, without the genetic code and the entire machinery of transcription and translation, DNA contains neither information nor meaning. Worse, strictly speaking, DNA does not even encode proteins— at least not functional proteins. DNA only encodes the amino acid sequence of a protein. The functionality of a protein comes from its three-dimensional shape and the physical properties of various parts of the protein. This shape is the result of protein folding, which is the result of
physical forces
(sometimes helped by chaperonins) acting on a sequence of amino acids. Much of the information to shape a protein into its functional form is contained in the laws of physics and the action of these laws in space and in time. How would you quantify the information input life receives from physics and space-time? You can’t. DNA only makes sense in the context of physical law, already-established order, and interactions with the environment. DNA does not tell us the final shape of an animal or a protein. Without context, DNA is meaningless.

An important statement of genetics is the
central dogma
: Information flows in only one direction, from DNA to RNA to proteins, never back from proteins to DNA. While the central dogma holds during replication, transcription, and translation, during the development of an organism, proteins control which parts of DNA are read at any stage of the development. There are feedback loops. The information to make a human being is therefore not encoded in DNA as in a blueprint. Although the word
blueprint
is often used for DNA, this is a misleading analogy. A much better analogy is
recipe
. To make a human being, DNA contains information to make proteins, which by their
physical interactions
with DNA, RNA, or other proteins, in the form of complicated regulatory feedback loops, shape the developing organism. This is similar to cooking a meal. A recipe does not contain a complete description of the result of cooking a meal; it just contains information about the ingredients (proteins) and the
timing of adding the ingredients (regulation). Then the physical interactions between the ingredients take care of making the meal.

Another way to put this is that organisms are emergent phenomena, emerging from complex interactions according to a specifically timed recipe. There is no way you could completely specify, in genetic code, every cell in a human being. How would you specify the trillions of connections in our brain? A few years ago, it came as a bit of a shock when the Human Genome Project revealed there are only about twenty-three thousand protein-encoding genes in the human genome. This is not much more than the number found in simple worms. I think the utter insufficiency of the information in DNA to specify an organism is one of the most powerful arguments for evolution. As argued before, life is a complex game played on the chessboard of physics and chemistry. I can think of no better analogy. Development of an organism needs information about proteins, but also needs space, time, physics, and complex feedback loops. None of these are encoded in DNA.