HOW THE LEOPARD GOT HIS SPOTS: Facilitated variation explains how animals, like this leopard, develop useful adaptations.
> (Source: Nicolas BennatoMorguefile)

Biologist Marc W. Kirschner is founding chairman of the systems biology department at Harvard Medical School where he and his colleagues study the temporal and spatial cues that affect embryonic development. With co-author John Gerhart of the University of California, Berkeley, he explores natural selection in the face of biology’s most recent discoveries in The Plausibility of Life: Resolving Darwin’s Dilemma, which was reviewed by University of California, Irvine evolutionary biologist Francisco J. Ayala in the April issue of Science & Theology News. 

With the release of the genome sequence in 2000, biologists finally realized that 22,500 is the magic number of genes needed to produce each person. That number is only one-and-a-half times that of a fruit fly and only six times the number in a bacterium — the simplest organism living on this planet. Looking at those genes, it was found that 15 percent were quite similar to those of bacteria, 50 percent were similar to those of a fruit fly, and 70 percent of flies were similar to those of a frog.

Humans are incredibly complex. Each person’s body contains about a hundred trillion cells and has probably thousands of cell types. So the question naturally arises: How do you get variety out of so few genes? How can animals be so different when many of the genes are the same? In short, where does novelty come from?

French naturalist Jean-Baptiste Lamarck had an answer to how diversity arises, especially in regard to the way variants become so well-suited to the conditions that exist in the environment. Lamarck thought that the environment caused the change. And this idea was so powerful that even though Darwin rejected it in The Origin of Species in 1859, 10 years later he embraced many of those same concepts. He agreed that the environment could in fact induce certain types of change. It took evolutionary biology many years to return to the ideas that Darwin had proposed in 1859 — that mutation is random, and that selection does not create variation but is merely a sieve that filters it.

This leaves a series of open questions: Is variation in anatomy and physiology, produced by random mutation, itself random? Or is it, in fact, biased? If it were biased, how could it be biased?

Our theory of facilitated variation is an effort to explain how animals convert random genetic variation into variation in structure and function that is biased to be most useful in evolution. Facilitated variation is not at all random. It doesn’t assume that need derives change, but it does explain why Lamarckian genetic variation produces nonrandom changes. Further, these changes are easily achieved with a rather small number of mutations, and, therefore, can happen quickly. They tend to be nonlethal because only nonlethal variation is inherited. And they tend to be appropriate to selective conditions. So even though mutation is random, change in the organism, physiology, anatomy and behavior can never be random. Change depends on what already exists.

There is a program on the Discovery Channel called “Monster Garage” in which host Jesse James shows how to convert a Ford Mustang into the world’s fastest lawn mower or a 1984 Porsche into a golf-ball retriever. But I doubt they could change a Cadillac into a violin. The point is that some changes are easy, while others are impossible.

What is easy? When you look into the processes, making a different-shaped limb, making a hand versus a flipper or a wing — that should be relatively easy to do. Making a larger brain, that should be relatively easy to do. Adapting to a different food supply, that should be rather easy to do. But the real insight that John Gerhart and I address in The Plausibility of Life: Resolving Darwin’s Dilemma is that on a cellular level, making new structures, even making a new eye, should not be that difficult either.

Constraints that empower

A key lesson from modern biology is that the animal is filled with genes and processes that do not change. Many of our genes are the same as a fruit fly’s. But these unchanging — and you might even say constrained — processes facilitate variation around them so that overall evolution is rapid.

I’ll give a couple of analogies. Imagine a monkey trying to write the word “monkey.” Give him a Bic pen, or even a Montblanc pen, and a piece of paper — he will produce only scratches on the paper. But give him a typewriter, and there will be a real possibility that he can pound out the requisite six letters in the right order in about 10 years. Not rapidly, but he could do it. The typewriter constrains the activity of the monkey to make letters, and letters have a chance to be useful. Pen scratches do not. If we constrain this monkey still further, using a computer program so that every time it punches a key it types a random English word out of the dictionary, it will probably produce the word “monkey” in less than a day — more constraint but more useful variation.

Let’s take a very common biological example, which is criticized by the people in the intelligent design community: the making of different kinds of vertebrate limbs. We have a great variety — we have our hands, we have bat wings, we have flippers, we have horse’s hooves. And if you think about it, making limbs seems rather difficult to achieve because not only do the bones need to be shaped in new ways but the muscles must also be appropriately attached to the bones in a new configuration. And that’s not enough. The nerve cells must be attached to the new positions where these muscles are.

That’s still not sufficient. A circulatory system that will appropriately nourish the bones must be generated, and the muscles and the nerve cells must be in their proper locations, along with a number of other simultaneous events.

It seems highly unlikely that this could happen until you look at the mechanisms by which the limbs were generated in the first place. When the bones are placed in some new location — and it can be done experimentally — the muscle cells will migrate out in an exploratory way from the flank of the body and take their position relative to the bones, wherever they are. As for nerve cells, nerve axons are produced in superfluous numbers, again exploring the periphery. If they attach to the right muscles, they will be stabilized and remain while those that cannot find muscles will die away and disappear.

The vascular system is another exploratory process that goes out into the periphery looking for regions with low levels of oxygen and, therefore, involves no preconceptions of where things are. If you look at the veins and the arteries in your right and left arms, which are genetically identical, you’ll see that they are quite different from each other because they have taken different random paths to explore the periphery.

Given that making a limb in the first place is much easier and changing a limb is much easier because the placement of the bones can be changed and the means by which the nerve cells attach to the muscles or the way the vascular system is generated does not have to be changed. These all adapt to the existing change.

Making new connections

A lot of evolution has to do with new connections between proteins and new connections between proteins and DNA. As it turns out, protein reactions can change easily and — in a way — that is quite useful.

As an analogy, imagine building a structure out of Lego blocks and building one out of modeling clay. Modeling clay is much more flexible, but with Lego blocks, which are each completely constrained, you can build the Eiffel Tower, or you can build a soccer ball. Although they are rigid, they have an easy connectability, which allows them to be arranged in new configurations. And that is similar to the way in which proteins and processes within the cell can easily interact in new configurations to generate new structures. They are rigid themselves, but they are “deconstrained” in the kinds of structures they can produce.

With the incredible numbers of cells and genes, there cannot possibly be genes or processes specifically for hands, brains or beaks. The processes that generate the structures of the body are more like carpenters or electricians or plumbers. They can build a beautiful church, or they can build a fast-food restaurant. They are versatile. And it is their versatility that makes it easy to understand change in evolution.

So the variety of tissues in our bodies is made largely from different combinations. The surprise in the last decade is that we now begin to understand what makes these things so combinable — the brilliance of a Lego block on a molecular level. Naturally, this ability to reuse different genes in new combinations, which is used within our bodies to generate new tissues, allows new uses in evolution.

I think that how molecular biology and developmental biology will help explain evolution and that will be the big story of the next decade in biology. But just as important is how evolution will help us understand ourselves.

Up until now, laboratory scientists have chosen to work on systems of limited variation — limited genetic variation, limited environmental variation. It’s easier to work in those systems. But in the future it will be the study of variation, whether normal or pathological, that will become the center of much biological study. Variation on a cellular level is critical to understanding human disease. We would dearly like to know how cancer cells vary so much and how they use their variations to evade the deadly poisons we throw at them.

Facilitated variation may have led to a conceptual completion of Darwin’s theory of evolution, but the subject of evolution and the study of evolutionary processes are far from complete. There’s a lot to learn. However, I hasten to add that it is only by testable scientific explanations that we will ever turn this understanding into something we can use for our own benefit. 

This essay is adapted from “The Plausibility of Life: Resolving Darwin’s Dilemma,” remarks delivered by Marc W. Kirschner at the Cambridge Forum in Cambridge, Mass. Used with permission.