The Genetic Factor

ONE TOOL KIT FOR ALL

NOVA: I want to get to the handwalkers, but to put their situation in context, can you first briefly describe the revolution in our understanding of genes and mutation that's taken place?

Sean Carroll: The revolution in understanding the role of genes in evolution really started a couple of decades ago with the first discoveries of the genes involved in building animal bodies. Those discoveries were launched from what may appear to be a fairly unexpected, humble place, and that was the fruit fly.

Geneticists were trying to get their hands around the genes involved in building body parts and sculpting the overall appearance of animals. And with the fruit fly, which was a workhorse of genetics for most of the 20th century, there was a whole catalogue of fascinating and bizarre mutants, very strange, with legs coming out of their heads or extra sets of wings or missing eyes.

So these were the result of mutations in one or more genes?

These were changes due to mutations in single genes. So the question that biologists had was: How could a single gene influence such a major feature of an animal? They started to track what genes these mutations were affecting and to isolate those genes. That led to a very rich understanding of how to build a fruit fly.

Now, that may not seem too exciting to anyone, but the unexpected revelation was that these very same genes that build fruit fly body parts build our body parts, mouse body parts, snake body parts, worm body parts, and the body parts of essentially all animals throughout the animal kingdom. That was really a shocking revelation to biologists, because the expectation was that very different animals with very different lifestyles and architectures would be built with different sets of genes. But the answer is no. Animals have very similar sets of genes, and this common tool kit exists throughout the animal kingdom.

So we humans are nothing special.

Right. The discovery that all sorts of animals—butterflies and zebras and mice and humans and snakes and fish—share a common set of body-building genes is deep, compelling, incontrovertible evidence of our common ancestry with all animals. While we humans may think of ourselves as something special and apart from the animal kingdom, this is a really strong signature that we are built along the same sorts of principles, using the same sorts of genetic materials that have been building the animal kingdom for 600 million years.

There is no single gene for humans walking upright.

So if animals are built using the same basic genetic tool kit, how is it that they come in so many different forms?

Well, we now understand that animal form is not so much a matter of the genes an animal has, but how they're used during the process of development, of going from a single egg to the complete mature animal, the building of all of its body parts. So these genes are used in every animal, but the choreography is what differs. And it's that different choreography between species that accounts for the endless forms of animals.

No gene for bipedalism

Could a single mutation—a twist on that different choreography—have caused the Turkish handwalkers to walk on all fours?

The central question is not really whether a single mutation could lead some individuals to walking on all fours, but rather whether a single mutation could lead normal apes walking on all fours to walking upright. And this is completely invalid. From what we understand from both genetics and the fossil record, the process of becoming upright involved all sorts of changes in our ancestors, in our skeleton and in our musculature, in various parts of the body (see Compare the Skeletons). And from what we understand about genetics of building those body parts and reshaping those body parts, it had to involve many genes and changes in those genes assimilated over a long period of time.

So there's no single gene for bipedalism.

There is no single gene for humans walking upright. Walking upright is something that was enabled by the collective actions of lots of genes remodeling our skeleton and musculature. It's just erroneous and you sort of miss the whole picture when you speak of a gene for bipedality. That's certainly going to be the case with things like speech and language as well. There's no single gene that if you have it you can talk, and if you don't have it you can't.

No genetic throwback

Could ancient genes for quadrupedalism be resurfacing in the handwalkers, as the Turkish scientist Uner Tan has suggested?

The interpretation that the members of this family are reflecting some sort of genetic throwback or some sort of ancestral situation—I don't agree with that interpretation whatsoever. They have a very serious defect in their cerebellum, and they are compensating for that balance problem by walking with the aid of their hands.

But, as you can see in the film, with some assistance they can stand upright. And you can see that other members of the family with the exact same anatomical defect and the exact same genetic lesion have walked upright to some degree. So there's just a very superficial resemblance. The fact that they're compensating by going on all fours does not at all mean that they are triggering, for example, some ancestral program for walking on all fours.

This story is fascinating, but it's likely to be no more than a piece of a really big puzzle.

Is this the same with those people born, for example, with monkey-like tails or an extra set of nipples? That it's not a throwback but just a mutation?

When we see individual humans with features that are not generally found in the human population—body hair in places we don't normally see it or extra sets of nipples or extra sets of ribs or extra digits on their hands—those are the result of genetic changes that have affected the choreography of development. The genes responsible for making those extra nipples or ribs have been around all this time. It's just they're being used in a little different way in those individuals, because they have a genetic mutation that affects how those genes are being used. So it's not some sort of throwback to an ancestor. It's just simply a malfunctioning of the genes that we and our ancestors have had that allows some superficial resemblance to a distant ancestor to appear.

So what gene or genes might have mutated in the handwalkers, if not for bipedalism?

The gene that's affected in the handwalkers certainly affects the development of the human cerebellum and perhaps more things. It's very common that these body-building genes affect multiple parts of the body. So it wouldn't surprise me at all that that gene, for example, plays a role in other parts of the brain. In fact, that gene could have played an interesting role at some point in the course of human evolution, anywhere from our very early split from a common ancestor from chimpanzees, or even in very recent human history. We don't know.

These first human genes being studied in-depth, those that affect brain size, those that affect language, those that affect locomotion in this case or cerebellum development, these are the first few stars in the telescope, in the human genome that we can see. But there are thousands more to investigate, and the power of the telescope is improving on nearly a daily basis. The access that we have to genetic history has exploded in very recent time, even just the last few months. So this is going to be an ongoing and expanding story of knitting together the whole picture of the genetic evolution of humans.

One piece of a big puzzle

How much might environment have played a role in the handwalking? That is, to what degree might their trait be due to nurture rather than nature?

I think a huge question we're going to confront in understanding human behavior is how much is genetically hard-wired and how much is affected by the environment or cultural. What we see in the handwalkers is that, okay, they have this walking on hands. But you can see with the brother who walks upright that it appears that the children experienced different rearing conditions, and that if given a chance to walk upright, and some assistance in walking upright, they would do so.

So while the siblings are genetically identical with respect to this mutation, they are not manifesting the same trait. Some are walking on hands, because they really haven't been given the assistance to walk upright, and another is walking upright. In general, we have to be very cautious about interpreting genetic mutations as imposing a strict limit on human behavior.

Might the Turkish family eventually tell us something about human evolution?

It might, but the way we're going to find out is by understanding what that affected gene does in terms of building the cerebellum, what other jobs it might have in building the brain or other parts of the nervous system. We're going to have to use other tools to understand what it might or might not have done in terms of the role in human evolution.

So is the excitement among geneticists about the handwalkers justified?

All the excitement about this family in Turkey and what this gene might hold is certainly understandable at one level. The researchers' excitement about it is akin to—imagine yourself as an archeologist working in the Valley of the Kings in Egypt. Every rock you look under, you're hoping to find a tomb, and every tomb you open, you hope to find a treasure.

Well, every geneticist is hoping that the box they're opening is the jackpot. But we should probably be more prepared to understand that there are lots of boxes we'll need to open, and the treasure's probably spread out over lots and lots of those boxes. It's natural for researchers to be thinking that they might have discovered a key link in some piece of history. But we have enough experience to be a little more sober than that about our expectations. This story is fascinating, but it's likely to be no more than a piece of a really big puzzle.